Horses are particularly susceptible to developing exertional rhabdomyolysis (ER) characterized by muscle stiffness, pain, and reluctance to move. Diagnosis requires establishing abnormal increases in serum creatine kinase activity when horses exhibit clinical signs. The 2 main categories of ER include sporadic ER arising from extrinsic causes and chronic ER that arises from intrinsic continuous or episodic abnormalities in muscle function. This article focuses on treatment of acute ER and causes and management of sporadic ER. Differential diagnoses for chronic ER as well as the pathophysiology, diagnosis, and management of recurrent ER, and malignant hyperthermia are also discussed in this article.