In recent years hyperhomocysteinemia has been established as a new risk factor for neural tube defects, arterial cardiovascular disease, and venous thrombosis. Concerning vascular problems, it first became clear that hyperhomocysteinemia might be (though not proven) a risk factor for arterial disease as observed in case-control studies, as well as in prospective analysis. More recently, the subject of hyperhomocysteinemia and venous thrombosis has received much attention. In this article, we discuss the issue of hyperhomocysteinemia, in general, the known causes of hyperhomocysteinemia and the association with venous thrombosis. Special attention is given to the value of the methionine loading test to diagnose hyperhomocysteinemia. An association of venous thrombosis and hyperhomocysteinemia has now been documented in several case control studies, but only in one prospective analysis. Thus far, there is limited evidence for a causal relationship for mild hyperhomocysteinemia in venous thrombosis. Briefly, the possible mechanisms of how hyperhomocysteinemia can lead to venous thrombosis are discussed. The article ends with therapeutic options to treat hyperhomocysteinemia (hyperhomocysteinemia can easily be treated with vitamins) and the description of a study that is presently being undertaken in an international multicenter design. This placebo-controlled study might resolve the question of whether lowering of homocysteine levels is of any clinical relevance in preventing recurrent venous thrombosis.