The past decade has shown a marked increase in the number of vaccines currently licensed and recommended for use in infants and children. Although most agree that it is desirable to combine as many of these vaccines as possible into a single injection, safety and efficacy must not be sacrificed. Clearly, a resurgence in Hib meningitis or measles (for example) would not be an acceptable price for the convenience of a single injection; but it is not clear how large a reduction in immunogenicity can be incurred without paying such a price. This conundrum has slowed the licensure of useful combination vaccines, despite a consensus that parents and practitioners have reached a limit to the number of injections they will deliver to young children. We anticipate US licensure for infant use of (at least) one DTaP-IPV-Hib vaccine and one DTaP-IPV-HB vaccine within the next few years, given the apparent lack of material reduction in immunogenicity of these specific combination products. Licensure in the United States of some of the other combinations now used in Europe is also possible, given supporting national surveillance data or improvements in our understanding of the correlates of immunity. Enhanced vaccination tracking systems and postmarketing efficacy surveillance should provide confidence that material reductions in efficacy could be detected following licensure, and thereby ease the approval of combinations that result in moderate, but perhaps immaterial, declines in immunogenicity.