Among various cardiovascular risk factors, hyperhomocysteinemia has recently emerged as an important one. While there are currently no doubts on the relationship between severe hyperhomocysteinemia and vascular disease, some uncertainty still persists on the relationship between mild hyperhomocysteinemia and vascular disease. Several group B vitamins, namely vitamin B6, vitamin B12, and folate, influence homocysteine metabolism, being cofactors of the main metabolic pathways which allow the disposal of this amino acid. There are also, however, suggestions from the literature that group B vitamins, and in particular vitamin B6 (pyridoxine/pyridoxal-phosphate), are modulators of cardiovascular risk independent of homocysteine. The results of a recent study of ours, with a long follow-up, indeed suggest that homocysteine and vitamin B6 are independent and additive cardiovascular risk factors.