Prophylactic vaccines are efficacious in preventing Human Papillomavirus (HPV) infection and subsequent cervical intraepithelial neoplasia (CIN), cervical cancer, other anogenital cancers, and anogenital warts. Female sex workers (SW) are at increased risk of acquiring sexually transmitted infections, including HPV. There are several reasons to offer HPV vaccination to SW: they are at high risk for HPV and often unvaccinated, and the immunogenicity of the vaccine is also excellent in previously HPV exposed women. Furthermore, women with disease caused by HPV may still benefit from vaccination. The efficacy of vaccinating mid-adult women (26-44 years old) against persistent HPV infection and CIN2+ is good. Although an SW may have been infected or exposed to HPV, she may not have been exposed to all vaccine-included hrHPV types. Vaccination induces mucosal immunity via the production of neutralizing antibodies on the surface of the female genital tract, thus preventing potential transmission to clients. Nevertheless, some considerations argue against offering vaccination to SWs. Current vaccines are only prophylactic and as such, do not affect current HPV infections. Women who have previously cleared HPV infections, may do so again and thus not need vaccination. Fewer SW might be naïve to HPV-types than currently thought. HPV vaccination has probably no effect on latent infections. Vaccinating sometime after sexual debut could be too late, as infections have already occurred. Taken together, some data suggest that vaccination of SW may offer health benefits, also for the community, but sufficient evidence is lacking. In certain cases, HPV vaccination of SW may be recommended. Evidencebased, public health decisions concerning vaccination of SW are challenging and could be facilitated with more research in this high-risk group.