Obesity is the most common nutritional disorder in the United States. Growing evidence suggests that obesity initiates a cascade of disorders including hypertension, diabetes, atherosclerosis, and chronic renal disease, many of which are interdependent. Abnormal kidney function, caused by increased renal tubular reabsorption, initiates volume expansion and increased blood pressure during excess weight gain, and the hypertension and metabolic abnormalities associated with obesity, in turn, contribute to chronic renal disease. Obesity causes cardiac and vascular disease through well-known mediators such as hypertension, type II diabetes, and dyslipidemia, but there is evidence for less well-characterized mediators such as chronic inflammation and hypercoagulation. Although obesity is increasingly recognized as a serious health problem, there are still many unanswered questions about how the multiple disorders associated with excess weight gain interact to cause cardiovascular and renal disease. Also, there are few studies that have examined whether sustained weight loss in obese subjects can reverse these changes. In view of the epidemic of obesity in our country and the excess burden of cardiovascular and renal disease in minority populations, addressing these issues is of paramount importance for the Jackson Heart Study, as well as for other national health initiatives.