Amniotic fluid embolism remains one of the most devastating conditions in obstetric practice with an incidence of approximately 1 in 40,000 deliveries and a reported mortality rate ranging from 20% to 60%. The pathophysiology involves an abnormal maternal response to fetal tissue exposure associated with breaches of the maternal–fetal physiologic barrier during parturition. This response and its subsequent injury involve activation of proinflammatory mediators similar to that seen with the classic systemic inflammatory response syndrome. Maternal treatment is primarily supportive, whereas prompt delivery in the mother who has sustained cardiopulmonary arrest is critical for improved newborn outcome.