In the city building game Afterlife, Hell's ultimate punishment for Envy is called the Escher pit and is designed to torture souls by having them all be given different punishments, and after a few days are allowed to switch with a neighbor, thinking he/she is better off, only to find that all punishments are worse than the last. The outside slightly resembles Relativity.
In the Futurama episode "I, Roommate", Fry and Bender go apartment-hunting and visit a room that resembles Relativity. Fry claims that he does not want to pay for a dimension he isn't going to use; Bender then trips down one of the stairs and continues to fall.
In the Drawn Together episode "Clara's Dirty Little Secret", Clara thinks she is pregnant, and Toot suggests that she fall down some stairs. Clara thinks of a suitable room and leads them to the "M. C. Escher room", where Toot pushes Clara down (and up, around, and back down) a flight of stairs.
A man (Andrew Lipson) created a Lego version of Relativity.
In the Family Guy episode "Brian Goes Back to College", Stewie and Brian share a room where Stewie puts up a framed print of Relativity, which he calls "Crazy Stairs." He then breaks it while playing Ultimate Frisbee and asks "Oh no, did that hit crazy stairs?". In a later episode, "No Meals on Wheels", Peter complains that the fact that his new restaurant is attracting paraplegics "is weirder than that rap video by M.C. Escher." Escher is then depicted inside Relativity dressed like MC Hammer in "U Can't Touch This". and rapping, "Going up the stairs and going down the stairs and going up the stairs and going down the stairs and going up the sideways stairs."
In the climactic scene of the film Labyrinth, Jareth the Goblin King takes Sarah to a stairwell that closely resembles Relativity, and walk as if defying gravity. A copy of the picture can be seen hanging on her bedroom wall earlier in the film. The Escher estate was given acknowledgment in the credits for the film.
In Xiaolin Showdown, a Xiaolin Showdown with Grandmaster Dashi vs. Omi the village morphs to something like the lithograph.
In Chrono Cross for the PlayStation, the second and third rooms of the Temporal Distortion area are based on Relativity. The first room is based on Van Gogh's works.
In the film Tomb Raider: The Cradle of Life the film's climax in the cradle also has several different gravity sources, which along with the lighting effects create a disorientating experience for the viewer.
In AdventureQuest Worlds, the first lord of chaos is Escherion, who has the ability to invert objects and lives in a castle with an inside similar to "Relativity".
In the video game Haunting Ground for PlayStation 2, there is a room modelled after the lithograph, complete with its inhabitants.
In the anime Yu-Gi-Oh!, the Millennium Puzzle, an Egyptian artifact owned by the protagonist, is said to contain the spirit of an ancient Pharaoh. The insides of the puzzle look remarkably like Relativity, which represents the Pharaoh's inability to remember his past. When various characters enter the puzzle during the course of the series, there are multiple gravitational pulls and strange dimensions (such as the instance when a main character, Joey, looks through a door, only to see himself inside looking through the same door some distance below).
In the game Gauntlet: Dark Legacy, the final level of the Dream Realm, known as the Maze of Illusion, is somewhat based around Relativity.
The it:X-Mickey comic Il giorno dei dimentiratti featured a chase in the center of the Relativity castle.
W.I.T.C.H. issue #74 features a fight in a house rearranged exactly as Relativity.
The Marvelcomic bookAvengers Forever #7 (June 1999) and the 2002 DC Comics book JLA/JSA: Virtue and Vice both feature a number of the story's superheroes finding themselves in a realm with multiple gravity sources assigned to different surfaces, much as in Relativity. In the former, the heroes almost immediately fall through space the moment they find themselves there. In the latter, they do not. Interestingly,[according to whom?] while the books were not written by the same author, both were illustrated by Carlos Pacheco.
In the manga Berserk, the realm occupied by the God's Hand demons resembles Relativity. The antagonists are able to bring themselves into that world, dubbed "Hell", through the use of the artifacts called Behelit.
The chorus of the Teenage Fanclub song "Escher" from the album Thirteen contains the lines "and I don't know if I'm going up or down", an apparent reference to the theme of this picture.
In the Walt Disney World version of Haunted Mansion, there is a room that reflects Relativity. It seems to go on forever, and has glowing, ghostly footprints ascending and descending the 'haunted' stairs.
In the Sprint commercial "Manning's Mind", Peyton Manning views multiple copies of himself running the stairs of a real-life version of Relativity.
The design of the Mines of Moria in the film adaptation of The Lord of the Rings: The Fellowship of the Ring was largely inspired by Escher's work, "Relativity" in particular. A scrapped sequence in The Two Towers involving an "Endless Stair" made specific reference to "Relativity" in its concept art.
The floors of Wayside School in the Canadian cartoon Wayside are depicted and based on this artwork, such as with sideways doors on walls and ceilings and stairs that can lead to another place or nowhere.
In the Phineas and Ferb episode Gaming the System, a video game level had staircases much like the ones in M.C. Escher's work, Relativity. In the episode The Doof Side of the Moon, as Phineas and Ferb were taking Irving's brother through a skyscraper they had just made, Phineas calls a room with the same staircases found in the print Relativity the M.C. Escher room. In another episode, "Where's Perry? Part II", Dr. Doofenshmirtz comments on how Major Monogram's sunglasses go on the same side of his nose (his eyes are depicted on the same side of his nose), asking if M.C. Escher actually made these. Monogram replies that M.C. Escher was a close family friend of his.
In a dream sequence within the film Inception, the architecture student Ariadne makes the streets of Paris bend and fold over themselves, forming a cube-like structure. In Christopher Nolan's shooting script for the film, the structure is described as having six perpendicular planes, with gravity functioning independently on each plane.
The CGI movie Mind's Eye contains one animation called "Prime Corporate Video", containing a colored 3D version of Relativity, showing the stick figure robots walking about and changing fields of gravity on their own.
Mott The Hoople"'s eponymous 1969 debut album features Escher's work Reptiles on its front cover.
In the film "Contact" the transport pod clearly resembles Escher's work Cube with Magic Ribbons, and there appear to be images from Reptiles on the inside of the rings that surround the machine.
The Doctor Who episode "Castrovalva" takes its name from Escher's early lithograph of the same name, though Escher's view of Castrovalva has none of the paradoxical elements of his later works to which the setting of the episode could more readily be compared.
The early nineties rock music group Chagall Guevara wrote a song called "Escher's World" which made many references to the impossible structures that can be found in Escher's work.
Escher is also the subject of a song by the rock group The Breakfast. The song is called "Escher's Etchings" and is included on their 2003 live album Bona Fide. The lyrics can be read here 
The music video for "Drive" by Incubus is based on Drawing Hands, beginning with an animated hand drawing a piece of paper and second hand to form the actual Escher drawing. It also shows the hand drawing lead singer Brandon Boyd to attach itself to. All drawings in the video were done by the band members themselves.
A comic crossover between Mike Allred's Madman and Bernie Mireault's The Jam, features Escher as a central character when the two characters enter into an alternate universe created by a somewhat godlike Escher, based on many of his works.
"Escher" is the title of a song by the British band Teenage Fanclub. The song is about a man who doesn't know if he is up or down.
In 2006 Audi released a commercial with many Escher-inspired scenes.
In the film Donnie Darko, the poster on Donnie's bedroom wall is M.C. Escher's "Eye".
In the film The Quiet Earth, Escher's Another World is seen on the wall of Zac Hobson's home during the surrealistic 'Effect Tremor' sequence. Given the subject matter of the film, the presence of the artwork is akin to a sly in-joke.
In the Psygnosis game "Lemmings", the 18th level of "Taxing" is named "Tribute to M.C. Escher", as the solution involves building a zigzag stairway slightly reminiscent of "Relativity".
The Flight of the Conchords song "Inner City Pressure" contains the lyrics, "You've lost perspective like a picture by Escher".
On the Joy Electric album, My Grandfather, the Cubist, there is a song titled "Draw For Me, M.C. Escher".
On the SyFy show Warehouse 13, Escher is said by the character Leena to be one of the architects, along with Thomas Edison and Nikola Tesla, who designed the Warehouse. There is also the Escher Vault, the design of which is similar to the lithograph Relativity. Inside this vault, the stairwells and walls are constantly moving. Anyone not wearing specially designed glasses run the risk of being lost forever once inside. H.G. Wells is the only known individual to have successfully navigated the Escher Vault without glasses, instead using her Inperceptor Vest to retrieve personal items stored within.
In the video game God of War III, the puzzle "Hera's Garden" is based on Escher's Waterfall.
In the 2010 science fiction film Inception, where Arthur gives Ariadne a tour of the dream world in which an Escher design can be seen faintly in the background.
In the 2010 Action/Adventure video game Dante's Inferno, the final part of the third circle, Gluttony, is depicted as a structure similar to the one featured in Another World, which the player must traverse in order to proceed to the next circle.
Progressive/fusion German band Kraan entitled the second track from their first LP "M.C. Escher"
Germand jam band United Jazz + Rock Ensemble entitled one of their tracks "Steps of M.C. Escher"
In the computer game "Diablo 2" the Arcane Sanctuary, an area in the 2nd act, is designed to resemble Escher's drawings; in fact the first thought you have when first entering that area is "Escher".
In the computer game Call of Duty Black Ops 2, a Zombies multiplayer map called 'Die Rise' is designed after his work.
The computer game The Bridge is themed primarily around Escher's works.
The computer puzzle game Monument Valley is a fully interactive interpretation of Escher's works, with as its goal to make architecture the protagonist. In order to win at this game, one must think like Escher from multiple perspectives.