Immune maturation is responsible for a progressive increase in antibody responses that can be elicited during the first year of life, such that neonatal immunization may currently not be expected to induce strong antibody responses. In contrast, B and T cell priming can be induced very early in life, without interference of maternal immunity. Strong IL-5 and IL-13 responses in young mice, and limited IL-12 and IFN-gamma release capacity by early life APC and T cells both in young mice and infants, could contribute to the severity of infections with intracellular pathogens in early life. It calls for evaluation of novel delivery systems, adjuvants and/or prime-boost immunization strategies capable to meet the challenge of both strong neonatal immunogenicity and acceptable reactogenicity. The extent to which early life murine immunization models may be useful for preclinical evaluation of infant responses is outlined in this review.