The incidence and mortality of acute pulmonary embolism (PE) remain ill defined, particularly in the setting of the emergency department. However, high-risk groups can be identified based on medical conditions known to predispose patients to venous thrombosis. Recent research into the physiologic regulation of coagulation and thrombolysis reveals that recurrent venous thrombosis and PE may be caused by heritable deficiencies and abnormalities of plasma proteins. To decide among options for evaluation and treatment of patients suspected of PE, physicians combine clinical assessment with patterns observed on radionuclide ventilation-perfusion (V/Q) scans. However, the prevalence of PE among patients with "low probability" V/Q scans suggests that current physician behavior may be imprudent. Heparin anticoagulation continues to be standard therapy for acute PE, but newer clot-specific thrombolytic drugs may offer superior benefits with acceptable complication rates in carefully selected patients.