The role of hyperhomocysteinemia as a cardiovascular risk factor has been a matter of debate of several decades. The present paper briefly describes the metabolism of homocysteine, the main genetic and acquired causes of hyperhomocysteinemia and the mechanisms presumably involved in the pathogenesis of cardiovascular and thromboembolic diseases. Current evidence-based data from epidemiological and interventional studies assessing the potential role of hyperhomocysteinemia in the occurrence of vascular complications are presented. Guidelines on screening and treatment of hyperhomocysteinemia are analysed in the context of daily practice of general practitioners.