Cardiovascular disease (CVD) continues to be a leading cause of death worldwide. Elevated serum cholesterol is one of the classical risk factors for CVD, which also include age, hypertension, smoking, diabetes mellitus, obesity and family history. Several therapeutic drug classes have been developed to treat hypercholesterolemia; yet, an important percentage of patients do not reach their treatment goals. Therefore, new cholesterol-lowering medications that have sites of action different from that of drugs available at present need to be developed. This review summarizes new information about cytochrome P450 enzymes 7A1, 27A1 and 46A1. These enzymes play key roles in cholesterol elimination and have the potential to serve as targets for cholesterol-lowering.