Obesity is becoming more prevalent in the developed world because of the abundance of food and the decrease of physical activity. Obesity is a risk factor for a host of diseases from arthritis to cardiovascular disease. The precise mechanisms by which obesity promotes cardiovascular disease are not well understood but are likely to include metabolic and inflammatory responses to the increased amount of stored fat. The endothelium plays a pivotal role in maintaining vascular health. Impaired endothelial function is an independent predictor of cardiovascular disease. Most studies of vascular function in obese subjects have demonstrated impaired endothelial function. This impairment of endothelial function becomes obvious early on, long before any vascular abnormalities become clinically relevant and detectable. Better understanding of the mediators of obesity-induced endothelial dysfunction may lead to the identification of new targets for interventions that may prevent or postpone the development of obesity-related cardiovascular disease.