It has long been known that the maternal diet, and therefore the nutrient supply to the developing oocyte, embryo or fetus, is one of the principal environmental factors influencing the development of the offspring. A reliable and balanced supply of amino acids, lipids and carbohydrates is required to support the high rates of cell proliferation and the key developmental processes that take place during the embryonic (pre-implantation) and fetal (post-implantation) stages of life. Eukaryotic cells have evolved a complex series of nutrient sensors that are able to regulate gene expression in response to imbalances in the supply of nutrients. In adults these systems serve two purposes; firstly to protect the cell from damage caused by acute deficiencies and secondly to optimise homeostatic control to deal with a prolonged excess or deficiency of a particular nutrient. This second process may have a critical impact on the long term health of the offspring. It has been proposed that adverse nutritional conditions during fetal development lead to adaptive changes in metabolism that lead to a ‘thrifty phenotype’ in the offspring (Hales and Barker 1992). Poor nutrition in early life produces permanent changes in glucose-insulin metabolism, including a reduced capacity for insulin secretion and insulin resistance (Hales and Barker 2001). However, if this ‘programming’ of metabolism during embryonic and fetal development is inappropriate for the long term nutritional environment it may lead to adverse long term sequelae for the offspring (Sayer et al. 2004, Yajnik 2004, Barker 2004). The initiating factor(s) for fetal programming may be nutrient(s) interacting directly with genes and their regulatory elements at the cellular level, altering patterns of growth and gene expression. In this review we will concentrate on some of the direct interactions between genes and nutrients and their possible influence on fetal development.