Guidelines for secondary prevention of ischemic stroke are being updated as research evidence continues to accumulate. The American Heart Association/American Stroke Association 2014 guidelines for secondary stroke prevention place greater emphasis on generalizability and clinical relevance, while being more specific to specific clinical situations, such as: atherosclerotic stroke, with an emphasis on statin lipid-modifying therapy and antithrombotic therapy; small vessel stroke, with an emphasis on antihypertensive therapy; cardiogenic embolism, where new oral anticoagulants are more effective than warfarin; intracranial atherosclerotic stenosis, where aggressive pharmacotherapy is preferable to endovascular intervention; and reducing plasma homocysteine levels and treating asymptomatic carotid artery stenosis, where aggressive drug therapy is preferable to endovascular intervention. Aggressive pharmacologic therapy is preferred over endovascular interventions for intracranial atherosclerotic stenosis, while lowering plasma homocysteine levels and screening for asymptomatic carotid stenosis still lack high-level evidence.