Dre's verse was written by then Aftermath artist, Hittman. The single's title harkens back to Dr. Dre and Snoop Dogg's classic smash hit "Nuthin' But a "G" Thang" from Dre's 1992 solo debut The Chronic in which Snoop Dogg instructs listeners at the end of the chorus to, "just chill, 'til the next episode,", the line itself being a reference to the song "It's My Thing," from the EPMD album Strictly Business, which in fact did not refer to this single but its predecessor, a leftover song from 1993 originally recorded for Doggystyle, but not included in its final version. The song has many references to 2Pac's "California Love", which he did with Dr. Dre while at Death Row Records, and To Live & Die in LA. Originally listed on the back cover of Doggystyle as "Tha Next Episode", the original version of the song was by Snoop Dogg featuring Dr. Dre, and had a much different beat and different lyrics. The original was 4:36 long, and referred to Dr. Dre's "Nuthin' but a 'G' Thang" numerous times. The background of the original was later used in Warren G's "Runnin' Wit No Breaks" on the Regulate...G Funk Era album.
The song's main sample interpolates David Axelrod's and David McCallum's "The Edge", borrowing from a brief segment at the beginning of the song, repeated in the middle of the song and in the end sequence. The song was sampled by R&B trio City High for their 2001 hit "What Would You Do". It was nominated for a Grammy Award for Best Rap Performance by a Duo or Group in 2001 for Dre and Snoop. The award, however, went to Dre and Eminem for "Forgot About Dre". The edit released for radio and music channels was heavily edited and had many re-recorded lines and muted censors as well as some removing the "smoke weed every day" part which Nate Dogg says at the very end. Barry Bonds used the instrumental section before the first vocals as his plate appearance music for a period of time during the 2000s. The Seattle Mariners' Chone Figgins has used the instrumental as his walk-up music during the 2011 season. Nate Dogg's line "smoke weed every day" is used in many internet memes. The song featured on video games Grand Theft Auto V on the station West Coast Classics.
A remix with the same name by Snoop Dogg and Lil' Mo appears on the mixtape DJ Felli Fel Featuring Snoop Dogg - The Heavy Hitters, which was released in 2002. A remix with the music from "Paradise City" by Guns N' Roses is available unofficially. A version dubbed by The Game as a diss towards 50 Cent was released in 2005. A remix entitled "TNE 2006" was released to radio airplay in 2006. It features Snoop Dogg & Nate Dogg. Joe Budden rapped over the beat during an appearance on DJ Green LanternSirius Satellite Radio show with Charles Hamilton. The prizefighter remix was released in 2002, featuring 2Pac, DMX and Nas. Joe Rickard, drummer for RED, is known to perform this song among other popular rap and hip hop songs live in concert in a medley. A version in Arabic appeared in the 2012 film The Dictator performed by Aiwa, Mr Tibbz, and actor Sacha Baron Cohen as the film's title character Admiral General Aladeen. In November 2014, trap music producer San Holo released a remix of the song, which has since garnered over 150 million views on YouTube.