The landscape of interventions to prevent transmission of sexually transmitted infections (STI), including human immunodeficiency virus (HIV), has changed considerably in the last decade. Of particular relevance to women are the licensure and uptake of highly effective immunization against genital human papillomavirus (HPV) and associated prevention against associated consequences, including cervical cancer; encouragement about the use of topical antiretroviral agents as pre-exposure prophylaxis to reduce risk of HIV and genital herpes acquisition; enhanced emphasis on expedited partner management and rescreening for persons infected with C. Trachomatis and N. Gonorrhoeae; and the availability of a modified female condom. While these advances are encouraging, effective prevention of HIV and the other STI remains a high priority, both internationally and domestically, and most urgently among women. Unaids reported in 2010 that while the rate of new HIV infections has fallen in several countries, these favorable trends are at least partially offset by increases in new infections in others; moreover, the proportion of infections in women is increasing in several countries, and young people ages 15–24 account for 41 % of new HIV infections in sub-Saharan Africa . In 2008, the CDC revised its estimates of the annual incidence of new HIV infections in the USA by 40 % (an increase from an estimated 40,000 new infections annually to approximately 56,000) . Moreover, a large proportion of new HIV infections continue to be diagnosed in late stages of the disease, and women are not exempt from these trends [3, 4]. As discussed below, rates of reportable non-HIV STI either have not declined or have actually increased in women. This chapter will review the current state of prevention interventions for HIV/STI in diverse populations of women.