Dietary calcium plays a pivotal role in the regulation of energy metabolism because high-calcium diets attenuate adipocyte lipid accretion and weight gain during the overconsumption of an energy-dense diet and increase lipolysis and preserve thermogenesis during caloric restriction, which thereby markedly accelerates weight loss. Intracellular Ca(2+) plays a key regulatory role in adipocyte lipid metabolism and triacylglycerol storage; increased intracellular Ca(2+) results in the stimulation of lipogenic gene expression and lipogenesis and the suppression of lipolysis, which results in increased lipid filling and increased adiposity. Moreover, the increased calcitriol produced in response to low-calcium diets stimulates adipocyte Ca(2+) influx and, consequently, promotes adiposity, whereas higher-calcium diets inhibit lipogenesis, inhibit diet-induced obesity in mice, and promote lipolysis, lipid oxidation, and thermogenesis. Notably, dairy sources of calcium markedly attenuate weight and fat gain and accelerate fat loss to a greater degree than do supplemental sources of calcium. This augmented effect of dairy products relative to supplemental calcium is likely due to additional bioactive compounds, including the angiotensin-converting enzyme inhibitors and the rich concentration of branched-chain amino acids in whey, which act synergistically with calcium to attenuate adiposity. These concepts are confirmed by epidemiologic data and recent clinical trials, which indicate that diets that include > or =3 daily servings of dairy products result in significant reductions in adipose tissue mass in obese humans in the absence of caloric restriction and markedly accelerate weight and body fat loss secondary to caloric restriction compared with diets low in dairy products. These data indicate an important role for dairy products in both the prevention and treatment of obesity.