Homocysteine has been identified as an independent risk factor for atherosc
lerotic and thrombotic disease. Both arterial (cerebrovascular, carotid, co
ronary, and peripheral arterial) and veno-occlusive disease, jointly termed
vascular occlusive disease (VOD) in this review have been associated with
hyperhomocysteinemia. In cases of homocystinuria, plasma homocysteine level
s are markedly elevated. In this setting, the association between homocyste
ine and VOD seems clear. However, in cases of mild to moderate homocysteine
mia, controversy remains regarding the association between homocysteine and
VOD, In part this controversy occurs because VOD has multiple etiologies,
Similarly, homocysteine levels are affected by several factors including vi
tamin status, age and gender, and genotype of the patient. The multiple eti
ologies of both VOD and hyperhomocysteinemia make controlled studies assess
ing their interrelationship difficult to perform, This review will attempt
to present studies that either support or rebut homocysteine as an independ
ent risk factor for vascular occlusive disease and will show that the study
of homocysteine and thrombosis remains an active area of research.