Pneumonia with secondary pleural infection causes considerable morbidity and mortality. Intrapleural instillation of fibrinolytic agents to dissolve fibrinous adhesions is intended to improve pleural fluid drainage and prevent pleural loculations. In the last 20 years their application in the every day clinical practice has dragged much of attention and several studies have supported their use in the management of parapneumonic pleural effusions (PPE) and pleural empyema (PE). However, recent published data cast doubt on the effectiveness of intrapleural fibrinolytic agents in promoting drainage of infected pleural effusions. Pending future clinical trials, fibrinolytic therapy may be used selectively in patients who fail drainage with appropriately sized, image-guided chest tubes if reasons exist to delay or avoid definitive surgical drainage. The scope of this article is to systematically review evidence for the efficacy of intrapleural fibrinolytic therapy in the treatment of PPE and PE with emphasis on controlled trials and present some of the future perspectives.