Neonatal animals are able to mount an effective immune response, both humoral and cellular, when immunized using conditions that maximize stimulation of antigen presenting cells, T cells, and B cells. In adults, somatic mutation is a key feature of the humoral immune response because it contributes to the generation of high affinity memory B cells. Recent evidence that B cells in neonatal mice and human infants can somatically mutate their immunoglobulin heavy chains suggests that neonates can utilize somatic mutation not only to diversify their restricted germline antibody repertoire, but also to improve upon this repertoire by the generation of B cells which can produce higher affinity antibodies. By extrapolation, if vaccination of children early in life resulted in somatic mutation and affinity maturation, this could provide a more protective antibody response to childhood diseases.