Epidemiological studies suggest that the perinatal environment can predispose human offspring to develop obesity and type 2 diabetes. Animal models provide a means of assessing the consequences of manipulating the perinatal environment in ways that cannot be done in humans. During the gestational period, maternal malnutrition, obesity, type 1 and type 2 diabetes, and psychological and pharmacological stressors can all promote, while early-onset exercise can ameliorate, offspring obesity and diabetes, especially in genetically predisposed offspring. Many of these perinatal manipulations are associated with reorganization of the central neural pathways which regulate food intake, energy expenditure, and storage in ways that enhance the development of obesity and diabetes in offspring. Both leptin and insulin have strong neurotrophic properties, so altered availability of either during the perinatal period can underlie some of these adverse developmental changes. Because perinatal manipulations can permanently alter the systems which regulate energy homeostasis, it behooves us to identify the responsible factors as a means of stemming the tide of the emerging worldwide obesity epidemic.