The etiology of statin myopathy remains unclear and concern about this toxicity is a leading reason that statins are underutilized. A number of observations suggest that this toxicity may be due to the metabolic effects of lipid-lowering in patients with minor muscle disorders. These patients have a high frequency of mutations for metabolic muscle diseases and often have depleted mitochondrial enzymes. Their exercise physiology and biopsy findings indicate reduced oxidation of fats and mitochondrial dysfunction. These subjects are often intolerant of other lipid-lowering therapies in addition to statins, which suggests that the myopathy is due to lipid-lowering itself more than a simple pharmacokinetic reaction to high statin levels. Altogether, these findings support the concept that statin myopathy is a metabolic muscle disease.