Abstract: Plasma homocysteine (Hcy) is an amino acid causing vascular injury. It is closely associated with endothelial cell injury, vascular smooth muscle proliferation, inflammatory responses, thrombosis and vascular calcification. An elevated level of Hcy may affect normal function of renal vasculature and glomeruli, thereby accelerating the progression of chronic kidney disease to end-stage renal disease. In maintenance hemodialysis (MHD) patients, the incidence of hyperhomocysteinemia (HHcy) is 33 folds that of normal individuals so that it becomes a common yet complex health issue. For accurately identifying HHcy and improving patient prognosis, this review summarized the common causes of HHcy in MHD patients and introduced various preventive and therapeutic measures.