We are now entering 'the second golden era of vaccines'. The first gave us many good vaccines, but some inadequately protective and some with unacceptable side-effects. Worse, we have no adequate vaccines against some of the most killing diseases in the world, such as tuberculosis, malaria and HIV. The development within this second golden era will build on the rapidly growing knowledge about the genetics of the immune system, uncovering the problems and possibilities of the variability of genes for HLA, cytokines and cell-surface receptors. Furthermore, we need to consider factors such as birth weight, gestational age, short- and long-term effects of breastfeeding, interference by helmith infestation and climate.