Chronic heart failure is a major public health problem causing considerable morbidity and mortality. Recent studies have shown that an elevated plasma level of homocysteine is a strong independent risk factor for heart failure, in addition to atherosclerotic disease. Preclinical studies have demonstrated that induced hyperhomocysteinemia acts via multiple pathogenic mechanisms, including inflammation and oxidative stress, to promote adverse cardiac remodeling and failure. However, clinical studies have not conclusively shown a causative relation between hyperhomocysteinemia and cardiovascular disease. This article will review current data concerning homocysteine and its pathogenic relationship to heart failure.