Statins, which act primarily to lower plasma LDL-cholesterol, are prescribed to reduce cardiovascular disease (CVD) risk, but treatment response is variable. Genetic variation may modify both statin efficacy and susceptibility to statin-induced adverse drug reactions. Pharmacogenomic studies of statin response using candidate-gene and genome-wide strategies have begun to uncover polymorphisms associated with statin-mediated changes in LDL-cholesterol and CVD risk. The contribution of individual genetic determinants to overall response variation is small, but the combined effects of multiple genotypes may be more substantial. Initial observations must be replicated across multiple statin clinical trials and in multiple population groups of differing race and ethnicity before they can be assessed for clinical utility.