Lessons learned from the successful end of endemic measles virus transmission (i.e., elimination) in the United States include the critical roles of strong political commitment, a regionwide initiative, adequate funding, and a broad coalition of partners. Implications of measles elimination in the United States for global measles control and regional elimination efforts include demonstration of the high vaccination coverage and, in turn, population immunity needed for elimination; the importance of accurate monitoring of vaccination coverage at local, state, and national levels; a vaccination strategy that includes at least 2 opportunities for measles immunization; and the essential role of integrated epidemiological and laboratory surveillance. The United States, with a population of 288 million, is, to our knowledge, the largest country to have ended endemic measles transmission. This experience provides evidence that sustained interruption of transmission can be achieved in large geographic areas, suggesting the feasibility of global eradication of measles.