Thrombolytic treatment accelerates the dissolution of thrombus in acute pulmonary thromboembolism (PTE) and is potentially a lifesaving treatment. High-risk PTE is the clearest indication for this therapy, and its use in intermediate-risk cases is still controversial. A PTE response team may enable a rapid and effective determination of risk and treatment in these controversial clinical cases. Approved thrombolytic agents for the PTE treatment are streptokinase, urokinase, and alteplase. Currently, the most widely used agent is alteplase. It has a short infusion time (2 h) and a rapid effect. Newer, unapproved agents for the PTE treatment are tenecteplase and reteplase. The active resolution of thrombus via thrombolytic agents improves rapidly pulmonary perfusion, hemodynamic defect, gas exchange, and right ventricular dysfunction. However, it is important to determine appropriate candidates carefully, to prevent hemorrhage, which is the most important side effect of these drugs. Catheter-directed thrombolysis seems to be an alternative in patients not eligible for systemic thrombolytic therapy.