The presence of maternally-derived antibodies at the time of immunization is known to interfere frequently with active immunization, with variable levels of clinical significance. Deciphering the rules as the basis of such inhibitory effects on infant vaccine responses would certainly contribute to the development of vaccination strategies for early life. These questions were addressed in murine neonatal or early life immunization models using various antigens (measles, tetanus, RSV) and antigen-presentation systems (peptides, proteins, live attenuated vaccines, live recombinant vectors or DNA plasmids) in the absence or presence of maternal antibodies. Factors identified as crucial determinants of maternal antibody-mediated effects on both live and non-live vaccines include the relative amount of maternal antibodies and of vaccine antigens present at immunization, antigenic conformation, epitope specificity and the distinct influence on B-cell and T-cell vaccine responses.