Extensive data implicate cholesterol in the atherosclerotic process responsible for coronary disease. Of the atherosclerotic disease outcomes, serum cholesterol is most strongly related to coronary disease. A significant relationship of serum cholesterol to all clinical manifestations of coronary heart disease has been demonstrated in the Framingham Study, after adjusting for coexistent risk factors. Cholesterol and blood pressure exert similar influences on the occurrence of coronary heart disease. Risk of coronary heart disease associated with serum cholesterol is continuous, graded, and strong, with ideal values for cholesterol probably in the 130-190 mg/dL range. The impact of serum cholesterol diminishes with advancing age, but the predictive value of cholesterol is restored when fractionated into its atherogenic LDL and protective HDL components. The predictive value of total cholesterol in serum at all concentrations, including values less than 200 mg/dL, can be enhanced by taking HDL cholesterol into account. The total/HDL cholesterol ratio is a practical, efficient means for evaluating the joint effect of the two-way cholesterol traffic. Other cardiovascular risk factors such as blood pressure, glucose, cigarette smoking, fibrinogen, and left ventricular hypertrophy markedly influence the risk associated with measured concentrations of serum cholesterol. In correcting hypertension or diabetes, lipid values are an important consideration in determining the urgency, type, and efficacy of treatment used. In contrast to coronary mortality, rates of overall mortality show a quadratic relationship to total cholesterol in serum, with excessive mortality at concentrations greater than 160 mg/dL.