Of the band's eight U.S. number-one singles on the Billboard Modern Rock Tracks chart up to that point, only one, "Can't Stop", from their 2002 album By the Way, was excluded, though the music video was featured on the DVD.

In 2011, drummer Chad Smith discussed the recording sessions for Greatest Hits, mentioning that the band had recorded 16 songs and wished to release an entirely new album just for this material after a brief tour; however, guitarist John Frusciante was heavily against this idea at the time, claiming that his playing style had evolved and changed too much, as had his musical influences.

"Bicycle Song" and "Runaway" appeared as bonus tracks on the deluxe edition of By the Way when it was released on iTunes in 2006 and can now be found on many other digital music stores.

"Rolling Sly Stone" and "Leverage Of Space" were included on the Live in Hyde Park album in 2004 and "Mini-Epic (Kill for Your Country)" was released as an "official" bootleg in 2015.

On February 7, 2014, in an interview with fans on Reddit, Smith claimed that the band hoped to one day release a box set including all unreleased material from the recording sessions for Greatest Hits.