Preclinical and human vaccine studies indicate that, although neonatal immunisation does not generally lead to rapid and strong antibody responses, it may result in an efficient immunological priming, which can serve as an excellent basis for future responses. The apparent impairment of CD4 and CD8 T-cell function in early life seems to result from suboptimal antigen-presenting cells–T cell interactions, which can be overcome by use of specific adjuvants or delivery systems. Although persistence of maternal antibodies may limit infant antibody responses, induction of T-cell responses largely remain unaffected by these passively transferred antibodies. Thus, neonatal priming and early boosting with vaccine formulations optimised for sufficient early life immunogenicity and maximal safety profiles, could allow better control of the huge infectious disease burden in early life.