In patients with essential hypertension and in those with diabetes mellitus, the presence of increased amounts of urinary protein or albumin has been shown to be an important and independent risk for an increased incidence of cardiovascular morbidity and mortality. A constellation of cardiovascular risk factors has been described in these individuals, as well as evidence for diffuse endothelial cell dysfunction, which suggests these individuals are particularly susceptible to the development of extensive vascular disease. Recent studies have also suggested that proteinuria is not only a marker for renal disease but it also predicts those patients at greatest risk for the development of chronic and progressive renal insufficiency. This effect of proteinuria was evident in patients in whom urinary protein excretion rates exceeded 1 g/24 hours, but probably is true even in patients with smaller amounts of proteinuria. This effect of proteinuria on progression of renal disease is independent of other risk factors such as level of renal function, blood pressure, and dyslipidemia. Recent clinical studies have demonstrated that modification of proteinuria by the use of angiotensin-converting enzyme (ACE) inhibitors independent of reductions in systemic blood pressure results in slowing of the rate of loss of renal function and even stabilization of renal function over longer periods of treatment. In patients with renal disease, the totality of evidence suggests that multiple pharmacological and dietary modifications will be necessary to achieve the optimal slowing of the progression of renal disease. In addition, strategies will be required to reduce risks involved in the development of cardiovascular disease to ensure optimal patient survival. The similarity of risk factors involved in cardio-renal disease progression should allow us to achieve this goal with our current therapeutic armamentarium.