Intrapleural tissue plasminogen activator (t-PA) has emerged over the past several years as a treatment option for patients with complicated parapneumonic effusion that does not respond to medical management and drainage. Fibrinolytics are thought to dissolve fibrin deposits and loculations within the pleural space, facilitating drainage of the trapped pleural fluid surrounding the lungs. Whereas older fibrinolytics (streptokinase and urokinase) have been studied for intrapleural use with conflicting results, t-PA is currently the agent most commonly used in adults for this indication. However, the literature describing t-PA therapy for complicated parapneumonic effusion and empyema is sparse, and studies have been highly variable in their methods. Several articles report use of this drug at doses ranging from 2-100 mg at daily intervals or more frequently. Surgical treatment options associated with good outcomes are also available to these patients. As a result, the indications for intrapleural t-PA (especially compared with surgical management) in patients with effusions resistant to conventional drainage are not fully clear. The usefulness of t-PA in all patients with resistant parapneumonic effusions or empyema before surgical intervention remains undetermined, but several studies have taken this approach. Sufficient evidence is available to indicate that this therapy does have potential in patients for whom surgery is not a safe or desired option. Further study is needed to better understand the role of t-PA and its optimal dosage in patients with complicated parapneumonic effusion.