After the success of their major label debut, Siren Song of the Counter Culture, and its single, "Swing Life Away", Rise Against returned to the studio in January 2006 to record their fourth studio album. The band had been writing songs and ideas during the Siren Song of the Counter Culture tour and had completed five songs by early December 2005. Also in December, it was announced that Bill Stevenson would produce the upcoming album at the Blasting Room studio in Fort Collins, Colorado. Pre-production began in January 2006 in Chicago. The album was recorded at the Blasting Room with producers Bill Stevenson and Jason Livermore for 12 weeks between January and April 2006. The band talked about the sound and release date of the album in April, saying, "We're pretty excited and can't wait for you to hear it. You won't find any acoustic guitar on this one, but perhaps a few other surprises and curveballs await your curious ears...look for an early summer release." The album's name was revealed in the same news release; it would be titled The Sufferer & the Witness. The album was mixed by Chris Lord-Alge in Los Angeles, and production was completed in April 2006.
The Sufferer & the Witness was released on July 4, 2006 and peaked at number 10 on the Billboard 200 album chart, the highest position the band reached at the time. Their highest charting album, Endgame, which was released in 2011 reached number 2 on the same chart.
The album received positive reviews, Corey Apar of AllMusic described the album "one shout-along, mosh-worthy song after another". He praised the music's "sincerity and passion" and described it "maturing within the realms of major-label hardcore revivalism, while still remaining relevant and exciting". The album received a rating of four out of five stars, while "Ready to Fall", the hugely popular "Prayer of the Refugee", "The Good Left Undone", and "Behind Closed Doors" earned Rise Against its heaviest airplay to date. The song "Under the Knife" appeared in the soundtrack for the 2008 Box office hit film Never Back Down.