Rhabdomyolysis (RML) is a rare and severe adverse effect of simvastatin (SIM). Several risk factors have been described which play a role in its pathogenesis, namely age >65, diabetes mellitus, renal disease, high-dose statin therapy, chemicals metabolized by cytochrome P450 3A4 or idiosyncrasy. Case summary: A 66-year-old man with diabetes, ischaemic heart disease and hypertension, on medication of CYP3A4 substrates amlodipine and alprazolam, maximal daily dose of SIM has been started for unknown cholesterol level. On the second day dark-brown urine, paraparesis, bile-like vomiting, on his fourth day of treatment total tetraparesis and oliguria characterized RML with acute renal failure. During his hospitalization of one-hundred-six days he underwent fourty-nine dialysis treatments. Sixteen months follow-up after discharge from hospital, his walking improved up to using one stick now. His cholesterol level is in physiological range with no statin therapy. Conclusions: On account of risk factors listed above this case should have been administered to low initial dose of SIM. Developing myalgia or weakness in muscles, treatment must be stopped. In a case of predisposition to RML statin therapy and dosage can only be performed under continuous supervision.