This Guidance Note has been developed to provide the UNAIDS Cosponsors and Secretariat with a coordinated human-rights-based approach to promoting universal access to HIV prevention, treatment, care and support in the context of adult sex work. Sound, evidence-informed measures to address sex work constitute an integral component of an effective, comprehensive response to HIV. The Guidance Note provides clarification and direction regarding approaches by the Joint United Nations Programme on HIV/AIDS to reduce HIV risk and vulnerability in the context of sex work. It provides a policy and programmatic emphasis that rests on three interdependent pillars: (a) access to HIV prevention, treatment, care and support for all sex workers and their clients; (b) supportive environments and partnerships that facilitate universal access to needed services, including life choices and occupational alternatives to sex work for those who want to leave it; and (c) action to address structural issues related to HIV and sex work. Further, it is firmly built on human rights principles supporting the right of people to make informed choices about their lives, in a supportive environment that empowers them to make such choices free from coercion, violence and fear. This Guidance Note affirms the human right to the liberty and security of person recognising each individual’s agency over her/his body and sexuality, as well each individual’s right not to be trafficked or held in slave-like conditions. It also affirms that all forms of the involvement of children (defined as people under the age of 18) in sex work and other forms of sexual exploitation or abuse contravenes United Nations conventions and international human rights law.