Hyperhomocysteinemia is a risk factor for cardiovascular disease in the general population. In chronic renal failure (CRF), plasma homocysteine levels rise when the glomerular filtration rate (GFR) is reduced 50%, and in uremia the majority of patients are hyperhomocysteinemic. The purpose of this study was to review possible mechanisms of homocysteine toxicity. Homocysteine, a sulfur amino acid found in blood in micromolar concentrations, can have toxic effects through a handful of general possible mechanisms. These mechanisms include oxidative stress (through the production of reactive oxygen species), binding to nitric oxide, production of homocysteinylated/acylated proteins, and accumulation of its precursor, S-adenosyl-homocysteine, a potent inhibitor of transmethylation reactions. Methyltransferase inhibition actually occurs in CRF and in uremia, and can have several functional consequences.