Plasma homocysteine concentration exhibits a strong relationship with (indices of) renal function. Hyperhomocysteinemia has been implicated in the high vascular event rate in patients with chronic renal failure. The precise pathophysiological explanation for the occurrence of hyperhomocysteinemia in renal failure is not yet elucidated. A defective intrinsic renal metabolism of homocysteine seems unlikely. There are several indications that whole body homocysteine metabolism is altered in renal insufficiency. Stable isotope studies in dialysis patients have shown a decreased homocysteine clearance by transsulfuration and decreased homocysteine remethylation and methionine transmethylation. Several, but not all, prospective studies have linked hyperhomocysteinemia to adverse cardiovascular outcomes in renal failure patients. Treatment of hyperhomocysteinemia in renal insufficiency is based on folic acid-containing regimens, but so far, none of the regimens has been shown to successfully normalize plasma homocysteine concentration. Intervention studies have not yet demonstrated beneficial vascular effects of homocysteine-lowering treatment in dialysis patients.