The first single from the band's third album, AB III, was "Isolation." The song was well received by music critics, who commended the band members' musical abilities, and it debuted at No. 34 on Billboard's Hot Mainstream Rock Tracks in October, despite the fact that the single was only published in the United Kingdom.
Unlike most Alter Bridge singles, it is both musically and lyrically highly heavy and aggressive, showcasing the band's style, as well as aspects of speed metal and a great melody, as critics have noticed. "A more cheerful track, with some actual metal in there – in fact, it has a speed metal bridge," guitarist Mark Tremonti said, adding, "It has a melodic chorus, though: melody is still the most important thing for us." About the song, Myles Kennedy said:
"I recall Mark Tremonti playing me the riff and the overall song, as well as some fantastic melodies. 'That's wonderful, that rocks,' I thought to myself. So, I believe that was quite early on. That was definitely one of my faves from the start when he and I started throwing ideas together, and I believe it was one of his as well because it's so aggressive and heavy."
Alter Bridge - Isolation - Meaning of the song
Lyrically, the song is a departure from the uplifting lyrics of most other Alter Bridge singles; it is about "the agony of feeling isolated" and how "the ability to love again can bring you out of it."Kennedy described the song as a continuation of the previous track on the album, "Slip to the Void." He said, "It's the idea that now you're isolated. You're in this new, dark place and how you deal with that and the repercussions of that." The rest of the album is a radical aberration from the band's first two albums in terms of subject matter. The song is also unique in that the main guitar solo is performed by Kennedy instead of Tremonti, although Tremonti performs two filler solos.