Secondary prevention including lifestyle modulation and medical interventions remain the basic principle in our therapeutic challenge to reduce the risk of recurrent subsequent ischemic stroke. The substantial number of randomized clinical trials published in the past 2 years was broadened our evidence-based therapeutic armament in the field of secondary prevention of ischemic stroke. An update of current knowledge in secondary stroke prevention is presented in this review on the basis of the 2007 revised guidelines of the German Neurological Society and the German Stroke Society. Special emphasis is given to medical and nonmedical modulation of cardiovascular risk factors (treatment of hypertension, hypercholesterolemia, and diabetes mellitus), prophylactic vitamin supplementation, and the use of platelet inhibitors and treatment of symptomatic intracranial stenosis.