Aims: To review clinical trials establishing the efficacy and safety of ezetimibe 10 mg once daily, as monotherapy and coadministered with statins, for the treatment of hypercholesterolemia. Methods and results: As monotherapy, ezetimibe produced reductions in low-density lipoprotein cholesterol (LDL-C) of approximately 18% ( P <0 ·01 compared with placebo). As add-on therapy for patients who failed to meet target reductions with statin monotherapy, the addition of ezetimibe produced a 21·4% additional reduction in LDL-C compared with statin monotherapy ( P <0 ·001). Addition of ezetimibe to statin therapy also significantly improved high-density lipoprotein cholesterol and triglyceride levels compared with statin monotherapy ( P <0 ·05, P <0 ·001, respectively). In four studies in which ezetimibe 10 mg was coadministered with simvastatin, atorvastatin, pravastatin, or lovastatin at different dosages, reductions in LDL-C levels with co-administration were significantly greater than those obtained with the corresponding statin monotherapy dose. Ezetimibe plus 10 mg of simvastatin or atorvastatin produced LDL-C reductions comparable to 80 mg of the respective statin monotherapy. In all the clinical trials, ezetimibe was well tolerated, with a safety profile comparable to that of statin monotherapy and to that of placebo. Drug‐drug interactions have not been observed when ezetimibe is given concomitantly with statins, fenofibrate, oral contraceptives, or a number of other commonly administered drugs. Conclusion: In the phase II and phase III clinical trial development program, ezetimibe has been shown to be an effective and safe new option for treating hypercholesterolemia even in difficult-to-treat populations such as homozygous and heterozygous familial hypercholesterolemia and sitosterolemia. (Eur Heart J Supplements 2002; 4 (Suppl J): J9‐J18)