Pulmonary embolism is an often underestimated, underdiagnosed, and undertreated disease. As symptoms and signs of pulmonary embolism are nonspecific, the diagnosis still remains a challenge to the attending physician. Diagnostic and therapeutic procedures depend on the clinical presentation of the patient. First we must suspect pulmonary embolism and consider its likelihood in the presence of a number of clinical signs and symptoms. Once pulmonary embolism is suspected, heparin should be administered. Additional basic support is mandatory if required. If the patient's hemodynamic situation is stable, available preferable noninvasive diagnostic options should be considered to confirm or rule out the diagnosis of venous thromboembolism before further administration of anticoagulant or thrombolytic agents. If the patient's status has deteriorated, bedside diagnostic techniques should be applied to reinforce the suspicion or establish the diagnosis. To restore pulmonary perfusion more rapidly than conventional anticoagulation is suspected to do, several dosing regimens of thrombolytic agents are proposed, with recent interest in short-term thrombolysis and bolus lysis with urokinase or recombinant tissue plasminogen activator. If thrombolysis fails or is contraindicated, catheter embolectomy or surgical embolectomy is indicated. The main therapy is prevention. In this article, clinical assessment, imaging techniques, and therapeutic options described in the published literature are discussed and clinical experiences of an emergency department with a noninvasive diagnostic approach are described.