Recent reports have suggested that the use of alcohol or drugs is related to sexual behavior that is high risk for HIV infection. If substance use leads to unsafe sexual activity, understanding the dynamics of this relationship can contribute to research and preventive and educational efforts to contain the spread of AIDS. In this article, we review research on the relationship between substance use and high-risk sexual behavior. We then consider the inherent limitations of the research designs used to study this relationship, outline some methodological concerns including measurement and sampling issues, and comment on causal interpretations of correlational research findings. We end with a consideration of potential avenues for future research and a discussion of implications of these findings for current AIDS prevention policies.