OBJECTIVE Statin therapy is the mainstay of lipid-lowering therapy; however, many patients, particularly those at high risk, do not achieve sufficient LDL-cholesterol (LDL-C) lowering. Thus, there remains an unmet medical need for more effective and well tolerated lipid-lowering agents. Guidelines recommend combining additional lipid-lowering agents with a complementary mode of action for these patients. One approach to complementing statin therapy is combination with inhibitors that block the intestinal absorption of dietary and biliary cholesterol. This review summarizes what is currently known about intestinal sterol transporters and cholesterol absorption inhibitors (CAIs). RESULTS The only lipid-lowering agent currently available that specifically targets an intestinal sterol transporter (Niemann-Pick C1-like 1) is the CAI, ezetimibe. It is effective in lowering LDL-C, both when given alone and when combined with a statin. Clinical outcome data with ezetimibe combined with simvastatin have recently become available, and definitive evidence that the incremental LDL-C lowering attributable to the ezetimibe component reduces cardiovascular events beyond simvastatin alone is currently under study. Other novel CAIs have been evaluated based upon the structure and properties of ezetimibe, but none remain in development. CONCLUSIONS Additional lipid-lowering agents are needed to fulfill an unmet medical need for those patients who do not achieve optimal LDL-C goals on statin monotherapy. The inhibition of cholesterol absorption is an important therapeutic strategy to reduce cholesterol levels. Based upon the demonstrated lipid-altering efficacy and safety of ezetimibe, several CAIs have been identified; all to date have been discontinued due to limited efficacy.