The intrauterine environment supports the development and health of offspring. Perturbations to this environment can have detrimental effects on the fetus that have persistent pathological consequences through adolescence and adulthood. The developmental origins of the health and disease concept, also known as the “Barker Hypothesis”, has been put forth to describe the increased incidence of chronic disease such as cardiovascular disease and diabetes in humans and animals exposed to a less than ideal intrauterine environment. Maternal infection, poor or excess nutrition, and stressful events can negatively influence the development of different cell types, tissues and organ systems ultimately predisposing the organism to pathological conditions. Although there are a variety of conditions associated to exposure to altered intrauterine environments, the focus of this review will be on the consequences of stress and high fat diet during the pre- and perinatal periods and associated outcomes related to obesity and other metabolic conditions. We further discuss possible neuroendocrine and epigenetic mechanisms responsible for the metabolic programming of offspring. The paper represents an invited review by a symposium, award winner or keynote speaker at the Society for the Study of Ingestive Behavior [SSIB] Annual Meeting in Portland, July 2009.