Increasing epidemiological evidence suggests that maternal nutrition and environmental exposure early in development play an important role in susceptibility to disease in later life. In addition, these disease outcomes seem to pass through subsequent generations. Epigenetic modifications provide a potential link between the nutrition status during critical periods in development and changes in gene expression that may lead to disease phenotypes. An increasing body of evidence from experimental animal studies supports the role of epigenetics in disease susceptibility during critical developmental periods, including periconceptional period, gestation, and early postnatal period. The rapid improvements in genetic and epigenetic technologies will allow comprehensive investigations of the relevance of these epigenetic phenomena in human diseases.