Ezetimibe is a synthetic 2-azetidinone that inhibits the absorption of sterols, including cholesterol, in the intestine. It is used as monotherapy or in combination with statins to reduce low-density lipoprotein cholesterol (LDL-C). Although extremely well-tolerated, there are reports of myopathy associated with ezetimibe. We performed a PubMed search through April 2008 to identify English language articles examining ezetimibe safety as monotherapy or in combination with other lipid-lowering agents. The incidence of musculoskeletal disorders in clinical trials using ezetimibe alone or in combination with statins is identical to placebo or the statin alone, respectively. We identified only six case reports of possible ezetimibe-associated myopathy. We concluded that ezetimibe neither produces nor exacerbates statin myopathy except, possibly, in rare cases.