For more than 20 years, moderately raised concentrations of total homocysteine have been associated with an increased risk of atherothrombotic vascular events but only recently has evidence mounted to suggest that the association may be causal. The association is independent of other factors, it is fairly consistent across many studies, it is strong and dose-related, and it is biologically plausible. However, the evidence needs to be strengthened by a systematic review of all comparable studies and the demonstration, in randomised trials, that lowering total homocysteine is followed by a significant reduction in atherothrombotic vascular disease. In addition, the measurement of total homocysteine needs to be standardised. If these can be achieved then total homocysteine measurement will become another useful marker of vascular risk, multivitamin therapy will be another therapeutic option for people at risk of atherothrombotic vascular disease, and fortification of food with folic acid will rise high on the political and public health agenda.