This article provides an overview of the HIV epidemic in Asia, the context within which the epidemic is evolving, and the key actions to address the challenges faced by countries and risk groups. HIV epidemics across Asia are predominantly concentrated among most-at-risk populations. Although there have been many successes in the HIV response in Asia over the past decade, great challenges clearly remain - especially when addressing most-at-risk populations, who are often criminalized, marginalized, and discriminated against. These groups face significant legal and social barriers to accessing HIV prevention and treatment services. In order to reach the Millennium Development Goal of halting and reversing the spread of HIV by 2015 and to achieve universal access to HIV treatment, these barriers must be overcome across Asia. High-impact programs must be targeted at those in need, with continuous and predictable funding for a sustainable response that incorporates prevention and treatment scale-up. Strong political leadership and the involvement of affected communities are key to developing a systematic and comprehensive response. The potential consequences of inaction in Asia are enormous: even small increases in the HIV prevalence levels in the region will translate into vast numbers of new HIV infections due to the sheer size of the population.