Cardiovascular risk factors have traditionally been divided into 2 categories: modifiable risk factors (smoking, hypertension, elevated cholesterol, reduced high density lipoprotein cholesterol, and diabetes), and nonmodifiable risk factors (age, gender, and hereditary factors). However, more recent data indicate clustering of several metabolic and familial factors that are often related to each other. A pattern of lipoprotein abnormalities characterized by increased hepatic production of apolipoprotein B-containing lipoprotein particles, high blood pressure, visceral obesity, and peripheral insulin resistance are identified with increasing frequency in subjects with premature coronary artery disease (CAD). The metabolic substrates for many such disorders are being uncovered, and genetic analysis of affected kindred have, often with conflicting results, suggested associations with candidate genes. In the context of a multifactorial approach, aggressive treatment of lipoprotein disorders in high-risk individuals, or in the secondary prevention of cardiovascular diseases, has resulted in a decreased rate of progression of CAD and a marked reduction in clinical events. Further work in the field of hemostatic factors has shown that fibrinogen, activated coagulation factor VII, spontaneous platelet aggregation, and elevated levels of plasminogen activator inhibitor-1 (PAI-1), are all associated with CAD. There is a strong association between lipids (especially triglyceride-rich lipoproteins) and fibrinogen, PAI-1, and activation of factor VII. In addition, vascular function, especially endothelial cell physiology, has been shown to be compromised in the presence of multiple risk factors and to be improved with intensive therapy aimed at reducing risk factors, especially plasma lipoprotein levels. The implications for clinical practice are important. In the primary prevention of cardiovascular disease, proper risk stratification must be carried out with specific attention given to lifestyle changes. Cessation of smoking and changes in diet (both qualitative and quantitative), exercise, and serenity are often required. In the prevention of cardiovascular disease in subjects at high risk, or in the secondary prevention of CAD, a clear justification exists for aggressive lifestyle changes, often coupled with lipid-lowering therapy and adequate blood pressure control. Basic research is providing us with a better understanding of the molecular interactions between lipoproteins and hemostatic factors. It is becoming increasingly necessary to develop novel pharmaceutical agents with the combined ability to reduce atherogenic lipoprotein levels while also reducing susceptibility to thrombosis.