The first months of life represent a period of heightened susceptibility to infection, but the immunological differences involved are as yet incompletely understood. T cell-independent B cell (antibody) responses are markedly compromised in the first year of life. T cell-dependent antibody responses mature much earlier, but neonates and infants may require multiple immunizations to achieve or sustain titers comparable to those in older individuals. Neonates can mount effective antigen-specific T cell responses, but CD4 T cell responses are often slower to develop, less readily sustained, and in general more easily biased towards a Th2 type response. The last observation likely reflects in part the less efficient capacity of neonatal dendritic cells to establish a milieu that favors a Th1 CD4 T cell response, but this limitation can be overcome given appropriate stimuli, as occurs in neonates immunized with bacillus Calmette-Guérin. We currently lack a clear mechanistic understanding of the molecular basis for these immunological differences between adults and neonates. The goal of ongoing and future studies is to generate the mechanistic insights needed to enable the rational design of vaccines and adjuvants for use in neonates and young infants, and thereby reduce the morbidity and mortality of infections early in life.