Amniotic fluid embolism is an uncommon, but potentially lethal, complication of pregnancy. Because amniotic fluid embolism usually is seen with cardiac arrest, the initial immediate response should be to provide high-quality cardiopulmonary resuscitation. We describe key features of initial treatment of patients with amniotic fluid embolism. Where available, we recommend performing transthoracic or transesophageal echocardiography as soon as possible because this is an easy and reliable method of identifying a failing right ventricle. If such failure is identified, treatment that is tailored at improving right ventricular performance should be initiated with the use of inotropic agents and pulmonary vasodilators. Blood pressure support with vasopressors is preferred over fluid infusion in the setting of severe right ventricular compromise. Amniotic fluid embolism–related coagulopathy should be managed with hemostatic resuscitation with the use of a 1:1:1 ratio of packed red cells, fresh frozen plasma, and platelets (with cryoprecipitate as needed to maintain a serum fibrinogen of >150–200 mg/dL). In cases that require prolonged cardiopulmonary resuscitation or, after arrest, severe ventricular dysfunction refractory to medical management, consideration for venoarterial extracorporeal membrane oxygenation should be given.