Almost 5 million people live with HIV in Asia. Although this number is relatively low compared to around 22 million people living with HIV in sub-Saharan Africa, which bears two-thirds of the total number of cases worldwide, the concentrated epidemic in Asia has global significance. Almost 2 billion people live in this region, and the HIV burden could become catastrophic if the number of people living with HIV increased by even a small percentage. Comprehensive and evidence-based prevention and treatment, as well as care and support for people living with HIV and their families, is urgently required to ensure an appropriate response to the epidemic. Although there are major challenges to ensuring universal access to HIV services in Asia, many of the barriers can be overcome if there is political will and civil society is adequately involved in the response. Human rights violations, the detention of large numbers of people, often for long periods and in poor conditions, simply for using or possessing drugs, the criminalization of HIV and of homosexuality in many countries, and stigma and discrimination continue to impede the national and global responses to the epidemic. A concerted effort will be needed to remove these barriers by changing legislation, policies, and practices. The global economic downturn has had a particularly devastating impact on low-income and middle-income countries and dropped millions of people below the poverty line. It will be critical to continue investing in prevention and treatment and, more broadly, in health systems in these countries, which already bear a disproportionate burden of HIV, malaria, and tuberculosis. Great progress has been made in recent years in the response to HIV and AIDS, but this progress remains fragile: a reduction in efforts now could jeopardize the good results achieved and allow AIDS to gain force again. We can still come close to, reach or even exceed, the health-related Millennium Development Goals by 2015. In particular, we can prevent millions of new HIV infections, dramatically reduce deaths from AIDS, and virtually eliminate transmission of HIV from mother to child in Asia – but only with targeted and expanded input from donors [1]. New evidence presented in this supplement sheds light on many of the key issues and challenges as we strengthen efforts to halt and reverse the HIV epidemic in Asia. Komatsu et al. [2] argue that resources should be focused on high-impact programs and on prevention, particularly for groups most-at-risk of HIV, such as people who inject drugs, sex workers, prisoners and pretrial detainees, and men who have sex with men (MSM). Transmission among these groups is still driving the epidemic across Asia, and yet they are often underrepresented, or even ignored, in the HIV response at regional and national levels. This needs to change if we want to reach universal access to prevention, treatment, care, and support. Other articles in this supplement focus on populations experiencing a rapid increase in HIV incidence, specifically MSM [3] and people who inject drugs [4]. These groups are often marginalized, demonized, and criminalized and programs for them are lacking or are not based on evidence and respect for human rights, a situation akin to that in eastern Europe, as described by Bridge et al.[5]. Other articles discuss the scale-up of HIV testing [6], the use of strategic information systems [7], and antiretroviral therapy [8] – all critical elements of a successful strategy to respond to HIV – illustrating shortcomings in the response and use of strategic information to develop a nuanced response to the epidemic. Although Thailand has been able to include antiretroviral therapy in universal health coverage and successfully expand access, this is not the norm across Asian countries. The Global Fund is an international financing institution that supports country-led programs for HIV, tuberculosis, and malaria, including those in Asia. We invest large amounts of funding to rapidly scale up life-saving evidence-based prevention, treatment, and care interventions. We strongly encourage countries to target their prevention interventions towards those most-at-risk of HIV. The rapidly evolving epidemic requires intensified efforts to enable countries in Asia to understand the dynamics and drivers of the epidemic. As the articles in this supplement demonstrate, the fight against HIV requires adequate financial resources, but also leadership and a willingness to address the many sociopolitical barriers that stand in the way of an optimal response to HIV in Asia. Acknowledgements The views expressed in this paper are those of the authors and do not necessarily represent the position of the Global Fund to Fight AIDS, Tuberculosis and Malaria. Conflicts of Interest: None.