The normal pericardial sac contains up to 50 mL of fluid, which consists of a plasma ultrafiltrate. Anything greater constitutes a pathologic effusion. The curvilinear pressure-volume relationship of the pericardial sac dictates hemodynamic consequences of a pericardial effusion and is responsible for rapidly accumulating fluid that causes cardiac tamponade. A variety of diseases and complications cause pericardial effusion. The most common are idiopathic pericarditis, cancer, connective tissue disorders, and hemorrhage. Management of pericardial effusion is dictated by whether tamponade is present or threatened. If it is, urgent/emergent pericardiocentesis is indicated. If not, a systematic approach to diagnosis and management should be undertaken.