Cancer is a multistage process requiring progressive genetic and epigenetic changes in neoplastic and responding stromal cells. Many alterations that occur during the process of malignant progression are regulated by the matrix metalloproteinase (MMP) family of extracellular proteases and their endogenous inhibitors. Recent work has identified a new cell-surface inhibitor of MMPs - RECK. RECK regulates MMP-induced pericellular signaling cascades during embryogenesis and tumorigenesis. Homozygous loss of RECK results in embryonic lethality and attenuated tumor development in adults - thus providing further support for an efficacious role for protease inhibitors as anticancer therapeutics.