Neoplastic pericardial effusion is a serious and common clinical disorder encountered by cardiologists, cardiothoracic surgeons, oncologists, and radiation oncologists. It may develop from direct extension or metastatic spread of the underlying malignancy, from an opportunistic infection, or from a complication of radiation therapy or chemotherapeutic toxicity. The clinical presentation varies, and the patient may be hemodynamically unstable in the setting of constrictive pericarditis and cardiac tamponade. The management depends on the patient's prognosis and varies from pericardiocentesis, sclerotherapy, and balloon pericardiotomy to cardiothoracic surgery. Patients with neoplastic pericardial effusion face a grave prognosis, as their malignancy is usually more advanced. This review article discusses the epidemiology and etiology, pathophysiology, clinical presentation, diagnosis, management, and prognosis of neoplastic pericardial effusion.