Ferroptosis is a new form of programmed cell death characterized by intracellular iron-dependent accumulation of lipid peroxide and primarily associated with iron metabolism, glutathione-dependent pathway, and Coenzyme Q10-dependent pathway. Recent studies demonstrate that ferroptosis is associated with central nervous system (CNS) diseases, such as stroke, Parkinson’s disease, Alzheimer’s disease, and Huntington’s disease. This review summarizes the key regulatory mechanisms of modulation of ferroptosis and its role in CNS diseases. These updates may provide novel prospective on therapeutical agent developments against CNS diseases.