Rhabdomyolysis is a medical emergency characterized by acute skeletal muscle breakdown with a sudden strong rise and subsequent fall of serum creatine kinase (CK) levels. Rhabdomyolysis events are provoked by exposure to external triggers, sometimes in combination with an increased genetic susceptibility. In this chapter, we will provide a summary on the etiology of exertional rhabdomyolysis and an overview of the triggers and genetic susceptibilities in adults with rhabdomyolysis, summarize the (sub) acute management of patients with exertional rhabdomyolysis, present a diagnostic approach to patients with exertional rhabdomyolysis, and provide recommendations for daily activities and sports after an episode of rhabdomyolysis to prevent a recurrent episode.