With heightened risks of HIV and other sexually transmitted infections, sex workers face substantial barriers in accessing prevention, treatment, and care services, largely because of stigma, discrimination, and criminalization in the societies in which they live. These social, legal, and economic injustices contribute to their high risk of acquiring HIV. Often driven underground by fear, sex workers encounter or face the direct risk of violence and abuse daily. Sex workers remain underserved by the global HIV response. This Series of seven papers aims to investigate the complex issues faced by sex workers worldwide, and calls for the decriminalization of sex work, in the global effort to tackle the HIV/AIDS epidemic.