A rotavirus vaccine was recently licensed by the Food and Drug Administration and is likely to be recommended for use in all infants by both the Advisory Committee on Immunization Practices and the American Academy of Pediatrics. If used as recommended, the vaccine is likely to prevent much of the 500,000 physician visits, 50,000 hospitalizations, and 20 to 40 deaths caused by rotavirus infections every year in the United States. An understanding of the biology, immunology, and pathogenesis of rotavirus infection will help to explain the strengths and limitations of the rotavirus vaccine.