Racial differences in the prevalence and incidence of HIV infection and AIDS diagnoses in the United States are striking. These differences have been recognized for nearly 20 years, yet they are not well investigated. In this article, we examine 15 factors identified in the sexually transmitted infection (STI) literature to explain the presence of racial/ethnic disparities in STIs. We review findings from these studies and offer suggestions for future research, with the goal of further understanding and reducing disparities in HIV. In general, the STI literature shows that an evaluation of individual behavior is necessary but insufficient on its own to account for racial/ethnic disparities in STIs. Population parameters should be included within models that traditionally include individual-level factors. The 15 factors can be categorized into 3 broad overarching themes: behavioral, prevention participation, and biologic explanations of differentials in STI transmission and infection. Future research that focuses on only 1 of the 15 factors discussed in this review, to the exclusion of others, is likely to yield poor outcomes. Conversely, an emphasis on the interactions of several factors is more likely to produce effective public health interventions and reductions in HIV transmission.