Malignant hyperthermia (MH) is a rare, life-threatening pharmacogenetic disorder of skeletal muscle metabolism, triggered by volatile anesthetics and succinylcholine. Its reported incidence ranges from 1 in 5000 to 1 in 100,000 anesthetics, and although historically associated with high mortality, the introduction of dantrolene and advances in high-fidelity critical care have reduced mortality to less than 5%. The disorder results from dysregulated calcium release through the skeletal muscle ryanodine receptor, producing an unchecked hypermetabolic state with tachycardia, hypercapnia, acidosis, hyperkalemia, rhabdomyolysis, and hyperthermia. Risk factors include genetic mutations in ryanodine receptor (RYR1) and calcium voltage-gated channel subunit alpha 1S (CACNA1S) receptors, family history of MH, and certain congenital myopathies. While patients with exertional rhabdomyolysis may share overlapping pathophysiologic features, data suggest that they are not universally at increased risk for MH, though some individuals harbor pathogenic RYR1 variants and may warrant further preoperative evaluation. By contrast, patients with Duchenne and Becker muscular dystrophy are not predisposed to MH but may develop fatal hyperkalemic cardiac arrest when exposed to succinylcholine or volatile anesthetics, necessitating strict avoidance of these agents. Diagnosis of MH is clinical, supported by end-tidal CO₂ monitoring, arterial blood gases, and laboratory data showing rhabdomyolysis. Prevention rests on preoperative risk stratification, trigger avoidance, and anesthesia machine preparation. Acute management requires immediate discontinuation of trigger agents, rapid administration of dantrolene, and aggressive supportive care. Importantly, a fever occurring more than 1 h after anesthesia and exposure to triggering agents is unlikely to represent MH and should prompt evaluation for alternative etiologies.