Pleural effusion is a frequent complication of acute pulmonary infection and can affect its morbidity and mortality. The possible evolution of a parapneumonic pleural effusion includes 3 stages: exudative (simple accumulation of pleural fluid), fibropurulent (bacterial invasion of the pleural cavity), and organized stage (scar tissue formation). Such a progression is favored by inadequate treatment or imbalance between microbial virulence and immune defenses. Biochemical features of a fibrinopurulent collection include a low pH (<7.20), low glucose level (<60 mg/dl), and high lactate dehydrogenase (LDH). A parapneumonic effusion in the fibropurulent stage is usually defined “complicated” since antibiotic therapy alone is not enough for its resolution and an invasive procedure (pleural drainage or surgery) is required. Chest ultrasound is one of the most useful imaging tests to assess the presence of a complicated pleural effusion. Simple parapneumonic effusions are usually anechoic, whereas complicated effusions often have a complex appearance (non-anechoic, loculated, or septated). When simple chest tube placement fails and/or patients are not suitable for more invasive techniques (i.e. surgery), intra-pleural instillation of fibrinolytic/enzymatic therapy (IPET) might represent a valuable treatment option to obtain the lysis of fibrin septa. IPET can be used as either initial or subsequent therapy. Further studies are ongoing or are required to help fill some gaps on the optimal management of parapneumonic pleural effusion. These include the duration of antibiotic therapy, the risk/benefit ratio of medical thoracoscopy and surgery, and new intrapleural treatments such as antibiotic-eluting chest tubes and pleural irrigation with antiseptic agents.