The biotechnology revolution has stimulated vaccine development, blessing us with new, safe, and effective vaccines, but burdening our vaccination schedule. The incorporation of multiple individual vaccines into combination vaccines can simplify vaccine administration programs and permit the inclusion of new antigens in the vaccine schedule. Although the development, evaluation, and implementation of combination vaccines pose numerous challenges and raise controversies that remain unresolved, there is a reasonable prospect of United States licensure within the next few years of several new combination vaccines for infant use. Approval in the United States of combination vaccines in use elsewhere might be speeded by improved vaccination tracking systems and post marketing efficacy surveillance, which would provide confidence that material reductions in efficacy could be detected following licensure, and thereby ease concerns regarding moderate, but perhaps immaterial, declines in immunogenicity seen with some combinations.