Pericardial effusion is a common finding in clinical practice either as incidental finding or manifestation of a systemic or cardiac disease. The spectrum of pericardial effusions ranges from mild asymptomatic effusions to cardiac tamponade. The aetiology is varied (infectious, neoplastic, autoimmune, metabolic, and drug-related), being tuberculosis the leading cause of pericardial effusions in developing countries and all over the world, while concurrent HIV infection may have an important promoting role in this setting. Management is guided by the haemodynamic impact, size, presence of inflammation (i.e. pericarditis), associated medical conditions, and the aetiology whenever possible. Pericardiocentesis is mandatory for cardiac tamponade and when a bacterial or neoplastic aetiology is suspected. Pericardial biopsy is generally reserved for cases with recurrent cardiac tamponade or persistence without a defined aetiology, especially when a bacterial or neoplastic aetiology is suspected and cannot be assessed by other conventional and less invasive means. A true isolated effusion may not require a specific treatment if the patient is asymptomatic, but large ones are at risk of progression to cardiac tamponade (up to one third). Pericardiocentesis alone may be curative for large effusions, but recurrences are also common and pericardiectomy or less invasive options (i.e. pericardial window) should be considered with recurrent cardiac tamponade or symptomatic pericardial effusion (either circumferential or loculated). The aim of this paper was to summarize and critically evaluate current knowledge on the management of pericardial effusion.