Female sex workers (FSWs) bear a disproportionately large burden of HIV infection worldwide. This article reviews available published data for HIV prevalence and incidence, condom use, and structural determinants among this group. To explore the potential effect of structural determinants on the course of epidemics, the authors use a deterministic transmission model to simulate potential HIV infections averted through structural changes in regions with concentrated and generalised epidemics, and high HIV prevalence among FSWs. This modelling suggested that elimination of sexual violence alone could avert 17% of HIV infections in Kenya (95% uncertainty interval [UI] 1—31) and 20% in Canada (95% UI 3—39) through its immediate and sustained effect on non-condom use) among FSWs and their clients in the next decade. Decriminalization of sex work would have the greatest effect on the course of HIV epidemics across all settings, averting 33—46% of HIV infections in the next decade. The authors conclude that multipronged structural and community-led interventions are crucial to increase access to prevention and treatment and to promote human rights for FSWs worldwide.