As the number of HIV infections in women has increased, there has been a concomitant recognition that prevention efforts to reduce sexual transmission must address the gendered context in which risk behavior occurs. This paper provides a longitudinal perspective on the emergence of the HIV epidemic in U.S. women and the parallel development of interventions to reduce risk. In the first portion of this paper, we briefly discuss the growth of the epidemic among women and how public health responses reflected the early discourse about infected women. We also address methods of protection available to women, and the emerging recognition of the importance of gender relations. In the second half of this paper, we show how gender-specificity in prevention efforts has evolved, using a framework developed by Geeta Gupta (2001) and relying on published reviews of the intervention literature in the past 10 years. Finally, we discuss in detail several recent examples. We conclude with a discussion of future directions.