Objective: The authors examined the changes in beliefs about the causes of and appropriate treatments for major depression between 1996 and 2006 in a representative sampling of U. S. adults. Methods: The authors compared data about depression from the mental health modules of the General Social Survey from 1996 ( 300 respondents) and 2006 ( 397 respondents), which measured perceptions of mental illness through use of vignettes. Results: There was an increase in the belief that depression is attributable to biological causes, from 77% in 1996 to 88% in 2006 (risk ratio [RR]= 1.14, 95% confidence interval [CI]= 1.04-1.23). Attitudes toward the treatment of depression changed as well, with 60% of respondents prioritizing a biological focus for treatment in 2006 compared with 48% in 1996 (RR=1.29, CI=1.04-1.59). These changes varied modestly by sociodemographic variables and were most pronounced among male, white, and elderly populations. Conclusions: There have been changes in attitudes about the causes and treatments of depression among the American public in the past decade, with a shift toward a biological framework. A greater understanding of beliefs about depression may lead to more effective outreach and education efforts. (Psychiatric Services 60: 306-312, 2009)