Technical Abstract: Metabolic imprinting occurs when nutritional influences during critical periods of development cause specific metabolic adaptations that persist to adulthood. Epigenetic mechanisms, which regulate the broad diversity of tissue-specific gene expression, are established during development and largely maintained throughout adulthood. Hence, to the extent that nutrition during development affects the establishment of epigenetic gene regulatory mechanisms, metabolic imprinting could occur via this mechanism. This article surveys the growing body of evidence that aberrant epigenetic gene regulation plays an important role in human disease, and recent data from animal models showing that subtle environmental influences during specific ontogenic periods can cause stable alterations in mammalian epigenotype. Experimental approaches are suggested to focus future studies of prenatal and early postnatal nutritional influences on developmental epigenetics in humans.