In this commentary, the authors highlight the findings of the meta-analysis by N. Crepaz and G. Marks (2001). The role of affect in sexual risk behavior, although intuitively obvious, is not well understood and has been largely ignored by HIV prevention researchers in favor of social-cognitive models of behavior. Crepaz and Marks synthesized the results from studies that have examined the relation of negative affect (e.g., depression, anxiety, anger) to sexual risk behavior and concluded that in the literature to date, these variables appear unrelated. The authors suggest that the Crepaz and Marks findings are not surprising given the methods used in the reviewed studies and suggest methodological approaches that will allow more sensitive analyses of the association between affect and sexual risk behavior.