Stroke is a leading cause of mortality and long-term disability worldwide. Survivors of a previous stroke or transient ischemic attack are vulnerable to further cerebrovascular events, as well as myocardial infarction, peripheral vascular disease, congestive heart failure and vascular death. Traditional approaches to the secondary prevention of stroke have included aspirin after ischemic stroke, warfarin for stroke associated with cardioembolic sources, and carotid endarterectomy for eligible candidates with significant carotid artery stenosis. In recent years, much evidence has emerged to support a broader array of pharmacotherapies, including newer antiplatelet agents, lipid lowering drugs, and several classes of blood pressure lowering therapies. Also under study are B vitamins for patients with cerebrovascular disease and hyper-homocysteinemia, and oral direct thrombin inhibitors for high-risk patients with atrial fibrillation. We review the literature to determine the clinical significance of these therapies, and provide recommendations regarding their use in the prevention of recurrent stroke.