Members of the plasminogen-plasmin (PP) system participate in many physiologic functions. In particular, uPA, its receptor (uPAR) and its inhibitor PAI-1 play an important role in cell migration, cell proliferation and tissue remodeling. Through a number of interactions, these components of the PP system are also involved in the pathogenesis of many diseases. In cancer, they modulate the essential processes of tumor development, growth, invasion and metastasis as well as angiogenesis and fibrosis. Thus, quantification of uPA, uPAR and PAI-1 in tumors and, in some cases in the circulating blood, became of potential value in the prognostication of many types of cancer. These include cancer of the breast, stomach, colon and rectum, esophagus, pancreas, glioma, lung, kidney, prostate, uterine cervix, ovary, liver and bone. Published data are reviewed in this chapter. Clinical validation of the prognostic value has also been made, particularly in cancer of the breast. Inclusion of these biomarkers in the risk assessment of cancer patients is now considered in the risk-adapted management in carcinoma of the breast. Factors limiting its broader use are discussed with suggestions how these can be overcome. Hopefully the use of these biomarkers will be applied to other types of cancer in the near future.