The Clinton Health Access Initiative, Inc. (CHAI) was founded in 2002 with a transformational goal: help save the lives of millions of people living with HIV/AIDS in the developing world by dramatically scaling up antiretroviral treatment. When CHAI was founded, many viewed this goal as unreasonable because health systems in poor countries were too weak and prices of relevant drugs and diagnostic tests were too high. CHAI played a leadership role, working alongside governments and other partners, to lower the costs of treatment and help build the in-country systems necessary to provide lifesaving treatment to millions of people. Since then, CHAI has pursued several similarly ambitious goals, from scaling up pediatric AIDS treatment in order to achieve equity with adults in a time frame few thought possible, to rapidly accelerating the rollout of new vaccines. CHAI has achieved many of its most important successes when seeking to fundamentally change the way the world approaches an issue and pushing the boundaries of what is considered feasible in global health. CHAI’s focus is transformational work that creates a fundamental change in the way actors approach and realize goals. To do this, the degree of impact of a CHAI program must be dramatic, the scale must be at the national or global level, the breadth must change the way others approach the problem, and the sustainability must allow for CHAI’s eventual exit without erosion of impact. Today, CHAI operates in 38 countries across the developing world and more than 70 countries are able to access CHAI-negotiated price reductions, vaccines, medical devices, and diagnostics.