Aim of this review is: (i) to describe the molecular mechanisms associated to statin induced myopathy including defects in isoprenoids synthesis followed by altered prenylation of small GTPase, such as Ras and Rab proteins; (ii) to present the emerging aspects on pharmacogenetics, including CYP3A4, OATP1B1 and glycine amidinotransferase (GATM) polymorphisms impacting either statin bioavailability or creatine synthesis; (iii) to summarize the available epidemiological evidences; and (iii) to discuss the concepts that would be of interest to the clinicians for the daily management of patients with statin induced myopathy.