The global health landscape changed dramatically after the adoption of the Millennium Development Goals (MDGs) in 2000. New financing mechanisms were created to channel funding from high-income governments and philanthropists towards the most solvable global health challenges, resulting in dramatically improved health outcomes around the world. That success has made a new level of ambition possible—the Sustainable Development Goals’ (SDGs) commitment to health for all—and new approaches to health finance are possible as well, including scaled-up domestic investments by middle-income countries. Our review of the new global health financing landscape suggests that at least 24 countries are likely to face significant changes in their ability to access external funding to priority health areas in the next 5 years, and that unless those changes are proactively managed and coordinated, the human toll could be dramatic. Our ability to maintain the health gains of the MDG era and expand them to all people depends on how global health stakeholders manage this wave of simultaneous transitions.