The first HIV (human immunodeficiency virus) case in India was detected in 1986 among female sex workers. The rapid spread in HIV infections subsequently due mainly to high-risk behavior among vulnerable population groups required a sensitive, multisectoral, multipronged response that had to influence risk behavior and alleviate the socioeconomic impact of the epidemic. The journey has been a unique one in many ways in the history of public health in India. The challenges emanated from the economic, social, legal, and cultural contexts in which risk-taking behavior took place, and to be effective, the response required a framework that had to be vastly different from the usual public health approaches adopted in the country. The fairly successful national response was made possible due to the presence and subsequent co-option of a vibrant civil society, which shaped discussions and discourses around sex, sexuality, and gender and could reach out to marginalized and stigmatized groups with messages and interventions. During the course of the thirty years of response to the epidemic, shifts in positions of individuals in the three organs of the government—executive, legislative, and judiciary—on key sensitive issues around sexual behavior and preferences could be discerned to some extent, which was unprecedented and helped strengthen the response. New infections have come down significantly over the years and treatment has scaled up massively. However, the momentum in national HIV programs has slowed down globally and in India, with lower finances and a shift to other national priorities. The sociocultural and economic contexts have yet to change for most of the groups vulnerable to HIV, and they will continue to determine risk behavior, requiring interventions to continue at a fairly high level of intensity.