Immunization is a great success of preventive medicine. In the United States, most vaccine-preventable diseases of childhood are at or near record lows while the number of diseases preventable by vaccination has increased. These successes result from a comprehensive system that includes basic research; developing and testing vaccine candidates; a manufacturing base; a regulatory authority; development of immunization policies; implementation of immunization recommendations; and a compensation system for the few people unavoidably injured by vaccines. Despite the successes, the system faces numerous challenges, including vaccine supply, cost, and safety; adult immunization; vaccine research and development; and biopreparedness.