Monitoring and evaluation (M&E) is fundamental to global HIV program implementation and has been a cornerstone of the President's Emergency Plan for AIDS Relief (PEPFAR). Rapid results were crucial to demonstrating feasibility and scalability of HIV care and treatment services early in PEPFAR. When national HIV M&E systems were nascent, the rapid influx of funds and the emergency expansion of HIV services contributed to the development of uncoordinated "parallel" information systems to serve donor demands for information. Close collaboration of PEPFAR with multilateral and national partners improved harmonization of indicators, standards, methods, tools, and reports. Concurrent PEPFAR investments in surveillance, surveys, program monitoring, health information systems, and human capacity development began to show signs of progress toward sustainable country-owned systems. Awareness of the need for and usefulness of data increased, far beyond discussions of indicators and reporting. Emphasis has turned toward ensuring the quality of data and using available data to improve the quality of care. Assessing progress toward an AIDS-free generation requires that the global community can measure the reduction of new HIV infections in children and adults and monitor the coverage, quality, and outcomes of highly efficacious interventions in combination. Building national M&E systems requires sustained efforts over long periods of time with effective leadership and coordination. PEPFAR, in close collaboration with its global and national partners, is well positioned to transform the successes and challenges associated with early rapid scale-up into future opportunities for sustainable, cost-effective, country-owned programs and systems.