World-wide, research initiatives are in progress to establish the role of the epigenome in human disease. Empirical data are still scarce, but particularly studies investigating how the epigenome links early developmental and adult disease may rapidly change this situation. Recently, several reports showed that prenatal environmental conditions are associated with persistent changes of the human epigenome. The evaluation of candidate loci among individuals prenatally exposed to the Dutch Famine indicates that such changes may be common but individually relatively small and may greatly depend on the timing of the exposure during gestation. These findings suggest that the epigenomic contribution to disease risk may entail the combination of multiple changes especially when adaptive responses are involved to cope with environmental conditions. Well-designed epigenome-wide studies will be crucial in creating a catalog of epigenomic regions that are sensitive to the prenatal environment to evaluate developmental influences on common human disease.