Atherosclerosis, the primary pathological condition accounting for most stroke syndromes, has been the intense focus of epidemiological, basic, and clinical investigations. Since these studies have direct bearing on the prevention of atherothrombotic brain infarction, this review emphasizes those advances in treatment resulting from their findings. The two most prominent theories on the pathogenesis of atherosclerosis relate to aberrations in lipoprotein metabolism and to enhanced proliferation of smooth muscle cells; likely, the theories are complementary. As a practical guideline for preventive therapy, the importance of using the total cholesterol level is stressed, although finer distinctions must rely on the low-density and high-density lipoprotein concentrations and their normalization. Since prevention of stroke may ultimately be its most effective therapy, consideration of cholesterol level, akin to strategies for preventing coronary heart disease, and efforts to avert platelet adhesion or aggregation and coagulation are warranted.