The spread of human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), tuberculosis (TB), and malaria across the world poses a major global health challenge. The international community has progressively recognized the humanitarian impact of these diseases, along with the threat they represent to economic development and international security. The U.S. has historically been a leader in the fight against HIV/AIDS, TB, and malaria; it is currently the largest single donor for global HIV/AIDS and has been central to the global response to TB and malaria. Over the past decade, Congress has demonstrated bipartisan support for addressing HIV/AIDS, TB, and malaria worldwide, authorizing more than $52.5 billion for U.S. global efforts to combat the diseases from FY2001 through FY2012. During this time, Congress supported initiatives proposed by President George W. Bush, including the President's Emergency Plan for AIDS Relief and the President's Malaria Initiative, both of which have demonstrated robust U.S. engagement in global health. Through the Global Health Initiative, President Obama has led efforts to coordinate U.S. global HIV/AIDS, TB, and malaria programs and create an efficient, long-term, and sustainable approach to combating these diseases. In 2011, there were significant scientific advancements in global health, including evidence that early HIV treatment not only saves lives but can reduce the risk of transmission by 96%. Despite this scientific landmark, these diseases remain leading global causes of morbidity and mortality. Many health experts urge Congress to capitalize on recent gains and bolster U.S. leadership and funding to combat these diseases. In contrast, some Members of Congress have proposed cuts to these programs as part of deficit reduction efforts. This report reviews the U.S. response to HIV/AIDS, TB, and malaria and discusses several issues Congress may consider as it debates spending levels and priority areas for related programs. The report includes analysis of: Funding Trends: Combined funding for the three diseases has increased significantly over the past decade, from approximately $832 million in FY2001 to $7.1 billion in FY2012. The bulk of the increase over time has been targeted toward HIV/AIDS, although in recent years funding for global HIV/AIDS has begun to level off. When compared to FY2011, funding in FY2012 included decreases for global HIV/AIDS, and slight increases for global TB and malaria programs. Some health experts applaud what they see as a shift toward less expensive efforts that maximize health impact. Other experts warn that divestment from HIV/AIDS could significantly endanger lives of those reliant on U.S. assistance and could reverse fragile gains made against the epidemic and other diseases. Disease-Specific Issues: HIV/AIDS, TB, and malaria each present unique challenges. Rising numbers of people in need of life-long HIV/AIDS treatment, as well as new evidence about the preventive benefits of early treatment, have heightened concern over the sustainability of treatment programs and incited debate over the appropriate balance of funding between antiretroviral treatment (ART) and other HIV/AIDS interventions. Growing rates of HIV/TB co-infection and drug-resistant TB strains have increased calls for escalating TB control efforts. Finally, growing resistance to anti-malaria drugs and insecticides threatens malaria control efforts, leading to calls for more attention to reducing resistance and developing new anti-malaria commodities. Cross-Cutting Issues: Several cross-cutting issues are currently being debated, particularly in relation to increased efficiency and sustainability of HIV/AIDS, TB, and malaria programs under the GHI. These include: Health Systems Strengthening; Country Ownership in Recipient Countries; Research and Development; Monitoring and Evaluation; and Engagement with Multilateral Organizations.