This paper examines the contributions of laboratory-based alcohol challenge research (ACR) to the development of HIV prevention interventions. Following a brief overview of HIV prevention interventions and related health behavior change models, we discuss how alcohol may influence mechanisms of behavior change. The paper highlights the value of ACR for: (1) elucidating mechanisms of action through which alcohol affects sexual risk behavior, (2) testing how alcohol may influence mechanisms thought to underlie HIV prevention interventions, (3) clarifying moderators of the causal influences of alcohol, (4) identifying novel intervention targets, and (5) developing strategies to reduce sexual risk among those who consume alcohol. We conclude with a discussion of the importance of using experimental research to identify mechanisms of behavior change that are specific to populations at high risk for HIV and outline some key implications for developing HIV prevention interventions that integrate the role of alcohol.