Many biological activities can be masked in globular and fibrillar proteins. Conformational or proteolytic changes can reveal these cryptic activities. In this review, we summarize the function of these unmasked fragments related to the coagulation/fibrinolytic pathways, and to pathological states involving the extracellular matrix proteins. The review also includes recent findings about the release of cryptic fragments from extracellular matrix proteoglycans.  For example, the tissue-remodeling processes that occur in vascular diseases, angiogenesis, and tumor invasion are dependent on the expression of these cryptic activities. These studies suggest that new therapeutic targets and agents, particularly those involving inhibition of angiogenesis, can be developed using recombinant molecules.