The U.S. Immunization Program has been one of the most successful efforts in preventive medicine. Since its beginning with passage of the Vaccination Assistance Act in 1962, polio, measles and rubella have been eliminated and many other vaccine-preventable diseases are at record or near record lows. In 1966, 3 years after licensure of the first measles vaccines, the Centers for Disease Control and Prevention began an effort to eliminate measles within the United States, an on-and-off effort that was to last more than 30 years. With measles elimination as the primary driver, fundamental components of today's immunization program were built that affected not only measles, but all of the vaccines and vaccine-preventable diseases of childhood. Some of the major contributions were the enactment and enforcement of immunization requirements for school attendance in all 50 states, enactment of an entitlement program for vaccine purchase, the Vaccines for Children Program, support for health services research to determine reasons for nonimmunization and interventions to improve coverage, development of standards for immunization practices and the measurement system for immunization coverage in all 50 states and 28 major urban areas. Key lessons have been: (1) the program must rest on a sound base of vaccine science and health services science; (2) having a limited number of measurable goals allows program focus, but consider strategies that have crosscutting impact; (3) accountability is critical to program performance at all levels-state, local and individual practice; and (4) establishing and maintaining political support is essential.