Fat embolization and the clinical syndrome associated with this pathology are poorly understood complications of skeletal trauma. Fat embolization is characterized by release of fat droplets into systemic circulation after a traumatic event. Fat embolism syndrome (FES) is an infrequent clinical consequence of fat embolization. Classically, FES presents with the triad of pulmonary distress, mental status changes, and petechial rash 24 to 48 hours after pelvic or long-bone fracture. FES incidence increases with the number of fractures sustained by an individual. Many clinicians believe that FES incidence has decreased over the past several decades secondary to advances in resuscitative measures. FES pathophysiology remains unclear. Current theories involve common mechanical and biochemical mechanisms that explain how fat emboli manifest as FES. Much controversy surrounds the question of whether there is a causal relation between intramedullary nailing and FES onset. Clinical diagnosis is essential, as laboratory and radiographic findings are nonspecific. Early supportive pulmonary therapy and other resuscitative measures may halt the pathophysiologic cascade and prevent clinical deterioration. Fortunately, if FES is diagnosed early, and pulmonary and cardiac functions are optimally supported, prognosis is very good.