High plasma levels of the amino acid homocysteine have been implicated in the development of vascular diseases, including stroke. Elevated plasma levels of total homocysteine (tHcy) above 15 μmol/L are present in less than 5% of the general population, but in as many as 50% of patients with stroke (and other atherothromboembolic vascular diseases). However, it remains uncertain whether a high tHcy level is a causal risk factor for stroke and should be lowered, or is a marker of another factor associated with stroke (e.g. acute tissue damage or tissue repair after an acute vascular event) and therefore should not be lowered. Plasma levels of tHcy can be lowered effectively by folic acid, vitamin B6 and vitamin B12 supplementation, and controlled trials have shown some beneficial effects on surrogate markers of vascular function. However, these markers are not established vascular risk factors or valid predictors of ‘hard’ clinical vascular outcome events. Until it has been shown in large randomised trials [such as the ongoing Vitamins to Prevent Stroke Study (VITATOPS) and the Vitamins in Stroke Prevention (VISP) study] that multivitamin therapy reduces the rate of recurrent stroke and other serious vascular events in patients with prior stroke or transient ischaemic attack, widespread screening for, and treatment of, high tHcy levels remains experimental and cannot be recommended.