Sex workers have been the protagonists and focus of HIV prevention campaigns and research since the late 1980s in Brazil. Through a review of national and international literature, combined with a history of sex workers' involvement in the construction of the Brazilian response, this article explores the overlaps and disconnects between research and practice in contexts of prostitution over the past three decades. We review the scientific literature on the epidemiology of HIV among sex workers and prevention methodologies. We conclude that although research focus and designs often reinforce the idea that sex workers' vulnerability is due to their sexual relationships with clients, their greatest vulnerability has been found to be with their nonpaying intimate partners. Few studies explore their work contexts and structural factors that influence safe sex practices with both types of partners. The negative effects of criminalization, stigma, and exclusively biomedical and peer education-based approaches are well documented in the scientific literature and experiences of sex worker activists, as is the importance of prevention programs that combine empowerment and human rightsbased approach to reduce HIV infection rates. We conclude that there is a need for actions, policies, and research that encompass the environment and context of sex workers' lives and reincorporate the human rights and citizenship frame that dominated the Brazilian response until the end of the 2000s. As part of HIV prevention efforts, female sex workers need to be considered above all as women, equal to all others.