Pericardial effusion is a relatively common complication associated with inflammatory and non-inflammatory diseases. The primary etiology of this condition could be considered when choosing therapeutic options and factors such as effusion size and its hemodynamic consequence. In most cases, small to moderate pericardial effusions can be managed with observation and anti-inflammatory medications unless the effusion develops rapidly. However, in a small proportion of patients, large effusions lead to impaired cardiac filling with hemodynamic compromise and cardiovascular collapse due to cardiac tamponade. The rate at which fluid accumulates is the primary determinant of hemodynamic impact and thus guides the choice of treatment, irrespective of the effusion's size. Severe cases are typically treated with pericardiocentesis with echocardiographic guidance. More aggressive treatments may be necessary for cases due to purulent or malignant etiologies. These cases may require a pericardial window to allow for long-term drainage of the pericardial fluid. This comprehensive review focuses on the epidemiology of pericardial effusion and discusses pathophysiology, diagnostic approaches, and therapeutic options for different causes of secondary pericardial effusions.