Observational data from prospective and retrospective studies indicate that elevated homocyst(e)ine (Hcy) is associated with preclinical markers of cerebrovascular disease and ischemic stroke. Although the exact mechanisms of this association are unresolved, data indicate that elevated Hcy promotes cerebral, arterial, and venous thrombosis, and may predispose to premature atherosclerosis and craniocervical arterial dissection. Plasma Hcy is a sensitive marker of low folate, B(12), and B(6) status. Data consistently indicate that folic acid supplementation in the form of vitamin tablets is the most effective strategy to lower mild-to-moderately elevated Hcy, with maximal benefit occurring in individuals with higher pretreatment Hcy or lower pretreatment folate levels. B(12) supplementation confers a minor additional benefit, whereas B(6) supplementation has not been demonstrated to confer further benefit. Despite reports that Hcy-lowering therapy may improve surrogate measures of vascular disease, the outcomes of clinical trials for secondary stroke prevention are pending. Until this information is available, we concur with the American Stroke Association guidelines for stroke prevention. Specifically, we recommend good dietary intake of foods rich in folic acid, B(6), and B(12) for primary prevention, and supplemental multivitamins (folic acid 400 g to 1 mg daily, B(12) 400 to 600 g daily, B(6) 2 to 10 mg daily) for individuals with known cerebrovascular disease and hyper-Hcy.