In 2012, the Global Commission on HIV and the Law called on countries to outlaw discrimination, repeal punitive laws and enact protective laws to promote public health and human rights for effective HIV responses. Today more than 89 countries have taken action to repeal or reform laws: some have repealed laws criminalizing HIV, same-sex relations, and drug possession, and others have enacted laws advancing reproductive rights, sex education, and the human rights of people living with or at risk from HIV. In 2015, at the United Nations (UN) General Assembly, countries unanimously adopted the 2030 Agenda for Sustainable Development (2030 Agenda). The 2030 Agenda, grounded in human rights principles, established an ambitious target to end the epidemics of AIDS and tuberculosis (TB). The 2030 Agenda made a bold pledge to leave no one behind. This Supplement highlights developments since 2012 in science, technology, law, geopolitics, and funding that affect people living with or at risk from HIV and its coinfections. The recommendations add to and amplify those of the Commission’s 2012 report Risks, Rights & Health, which remain as relevant as they were six years ago.