The set list has been described as containing well-known songs by 'an impressive collection of artists' such as Van Halen, Jimi Hendrix, Metallica, and Tool.

Once a player or band has access to a song via any instrument or band Career mode, that song can be played in Quickplay mode or any of the other competitive modes in the game. The player or band must complete easier gigs before the more difficult gigs are available. These gigs are arranged approximately based on the difficulty of the songs in that gig for the selected instrument or band, with more difficult songs appearing in later gigs. In the single player and multiplayer band (Career Mode) modes, songs are distributed into various 'gigs' that contain between 3 to 6 songs each gigs may also contain a boss battle (for the single player guitar career) and encores that are revealed once all the other songs in the gig are completed. The game disk contains 86 songs, all of which are master recordings-a first for the Guitar Hero series.

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