Ezetimibe/simvastatin is a combination of a statin and a cholesterol absorption inhibitor. This article reviews current information on the pharmacology, clinical efficacy and safety of ezetimibe/simvastatin combination therapy as a lipid-lowering pharmacologic option. Focus is on the LDL cholesterol-lowering efficacy of ezetimibe/simvastatin. PubMed was searched for english-language articles from January 2005 to 14 April 2010 using the keywords 'ezetimibe and simvastatin' and 'hyperlipidemia'. Reviewers screened all records and only English language papers and human clinical studies were included in the review. References of these papers were reviewed for relevant articles, and retrospective studies were excluded. Limitations include the exclusion of non-English publications, the use of only one data source (PubMed), and the fact that most studies were of short duration and several studies were of low quality (nonrandomized trials or meta-analyses). Ezetimibe and simvastatin has proven to be a well-tolerated, effective lipid-lowering drug combination. It is effective in reducing LDL-cholesterol and triglycerides, and increasing HDL-cholesterol. It also decreases C-reactive protein and exhibits some pleiotropic effects in a variety of patient populations. More data are needed to evaluate its effect on cardiovascular events/outcomes.