This article will review the results of recent clinical studies relating to the pericardial fluid in patients with various heart diseases. In ischemic patients, several angiogenic growth factors are accumulated in a high concentration in pericardial fluid. These may contribute to the angiogenesis and arteriogenesis, which are self-protecting mechanisms of myocardial ischemia. In congestive heart failure, natriuretic peptides are released into the pericardial fluid in a higher concentration compared with plasma levels. This suggests that these peptides may act as autocrine and/or paracrine factors. Pericardial fluid from ischemic patients induces cell proliferation and apoptosis depending on the cell type. Intrapericardial drug administration may provide a reasonable therapeutic strategy for heart diseases. In conclusion, the analysis of pericardial fluid appears to be a logical approach for elucidation of the pathophysiology of the heart.