Multiple studies have shown that the intrapleural instillation of fibrinolytic agents provides an effective and safe mode of treatment for complicated parapneumonic effusions and empyemas that decrease the need for surgical interventions. Although most investigators use streptokinase and urokinase, the technique of instillation is not standardized. The usual dose of streptokinase is 250,000 IU, but doses range from 50,000 to 220,000 IU for urokinase. Reported success rates range from 38% to 100%, but outcomes depend on the stage of progression of the parapneumonic effusion when fibrinolytics are employed. Fibrinolytics are more effective in complicated parapneumonic effusions than in established empyemas. Although complications of fibrinolytic therapy rarely occur, they result most often from allergic reactions to streptokinase. Urokinase is safer but more expensive. More randomized, comparative, controlled studies are needed to further define the most effective mode of fibrinolytic therapy for subgroups of patients with pleural infection.