In 2003, the band signed with their first label, Doghouse Records. A year later, they released ...Is a Real Boy. To support the album, they picked up new members and began touring; however, despite rapidly growing critical and fan acclaim, Bemis' health problems, including bipolar disorder and drug addictions, sidelined the band in 2005 as five band members left during the year.
Say Anything signed with J Records in 2005 and, following Bemis' successful rehabilitation, re-released ...Is a Real Boy on J Records. They went on co-headlining tours with Saves the Day in 2006 and Hellogoodbye in 2007. On October 23, 2007, the band released their third full-length album, In Defense of the Genre. In 2008, Say Anything went on a headlining tour across the US and UK and appeared on every date of Warped Tour. Their fourth album, entitled Say Anything, was released in November 2009. I Don't Think It Is, the group's most recent album, was released in 2016.