Data from studies on the benefits of statins in coronary artery disease patients in preventing recurrent primary and secondary cardiac endpoints, as well as ischemic strokes, imply the potential value of statins in recurrent ischemic stroke prevention without coronary artery disease symptoms or, by extension, primary ischemic stroke prevention. However, data on the latter are lacking, although the ongoing Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) study is designed to answer that question. Until these data become available, clinicians are justified in using statins to avert recurrent ischemic strokes due to atherosclerosis, especially if elevated total cholesterol, increased low-density lipoprotein cholesterol, and/or reduced high-density lipoprotein cholesterol, as specified in the National Cholesterol Education Program Third Adult Treatment Panel, are present. This article reviews the pathophysiology of atherosclerosis, particularly the major components of atheromas of cholesterol, smooth muscle cells, inflammation, "foam cells," and connective tissue elements. Emphasis is placed on the first three and the results of statin trials in coronary artery disease, as well as the beneficial pleiotrophic effects of statins in ischemic strokes.