Rhabdomyolysis is a rare potentially dangerous syndrome resulting from the dissolution of skeletal muscle fibres. An isolated attack of rhabdomyolysis can have various causes, such as trauma, hyperpyrexia, infections, electrolyte imbalances, seizures, severe exertion, and drugs or substance abuse or a combination of these. Recurrent episodes and/or a family history of rhabdomyolysis is more likely caused by an underlying genetic defect. Three patients with rhabdomyolysis are described. One patient had an isolated episode due to excessive exercise. The other patients had a medical history or accompanying symptoms that suggested an underlying genetic metabolic myopathy confirmed in both by DNA analysis. An algorithm on when and how to screen for underlying genetic diseases is presented. Diagnosis of these genetic diseases is important for adequate counselling and dietary measures to prevent future episodes.