Obesity and type 2 diabetes are increasing in prevalence, bringing with them considerable morbidity and mortality. The pathophysiology of each condition is quite complex and incompletely understood. Many hormone-like signaling agents that affect energy metabolism are released from adipocytes (eg, leptin) and from immune cells (eg, tumor necrosis factor-alpha). Type 2 diabetes and obesity are each characterized by the strong interaction of genetics and environment over time. A few single-gene defects have been found that lead to these conditions, but in most cases there is a polygenic contribution. In addition, several environmental factors such as lifestyle, social influences, and fetal surroundings may lead to development of these health problems. Genetic and environmental factors associated with these disorders are explored.