The songs have been divided in two discs: the first one, dubbed "The Dark Side", features heavy, metal-influenced songs, while the second one, entitled "The Light Side", spotlights the band's melodic side. The set spans the years from 1991 to 2005, therefore it doesn't include any songs from Dream Theater's debut album, When Dream and Day Unite, their A Change of Seasons EP (although it was released in 1995) or their 2007 release Systematic Chaos.
Former drummer Mike Portnoy explained in the album's booklet that the selection of songs were carefully made in order to appease both the newcomer and the already existing fan by offering up different versions of songs on other albums to "make the newcomer want to buy the albums from whence they came" and to "give different versions of songs already on other albums" to the current fan. He also suggests that a third disc should've been included called "The Epic Side", showcasing their progressive side.
The album's booklet is missing credits of "As I Am" and the songs from Octavarium as edited versions; those tracks are actually shorter than the ones from that album as secondary versions for "As I Am" (also a clean edit), "The Root of All Evil" and "Sacrificed Sons" with the first minute intro taken out, "The Answer Lies Within" has the first 15 seconds of bells ringing taken out, "I Walk Beside You" has the same length as its original album but with the clock ticking sound taken out of the first riff.
On the album cover, on the words "Greatest Hit", some letters are printed in red, being the "s" from Greatest and the word "hit", making the word "shit". And in the parenthesis at the bottom, the number "21" in "(... And 21 other pretty cool songs)" is also in red, possibly meaning that there's one "Greatest hit", while the other 21 compared, are "shit"