The renowned global health leader, Peter Piot, LSHTM, opens this conversation with reflections on what drove the historic global health successes, including “a brilliant coalition” and U.S. bipartisan leadership grounded in statecraft and strategic thinking. That “twenty-five years of historical anomaly” has however now ended. In Europe, that shift has resulted from populism combined with intense migratory pressures, the costs of battling the threat of Russia, and the high costs of providing a social safety net for a rising elderly population. Global Health 2.0 will be built on health sovereignty in Africa, Latin America and Asia. The shock scarcities of the Covid pandemic had already awakened the need for greater self-reliance; the sudden and abrupt decline in donor funding for global health is the latest shock. We will see “sunset clauses” and “mergers and acquisitions” across many familiar international institutions. AI promises innovations in R&D and delivery, aided by philanthropies. Centers of excellence are now in place “everywhere.”  It is “no longer a one-way street.”