In the United States, there continues to be high incidence of HIV infection among men who have sex with men (MSM), who represent 57% of new infections in 2009. While many studies report associations between non-injection substance use and sexual risk behavior among MSM, overall results are mixed. Summarizing these studies is difficult because researchers have used a variety of assessment periods for substance use and sexual behavior. We review the scientific literature on event-level measures, which assess substance use and sexual risk behavior immediately before or during a sexual encounter and provide the most precise link between these two behaviors. From January 2009 through March 2010, we searched four databases: Ovid (MEDLINE and PsycINFO), Web of Knowledge, and Sociofile. Across studies, results varied by substance with little within substance consistency or a lack of research except for two notable exceptions: methamphetamine and binge alcohol use. The findings underscore the importance of providing HIV risk-reduction interventions for substance-using MSM.