Pericellular proteolysis is a hallmark of tumor cell metastasis. The membrane type (MT)-matrix metalloproteinases (MMPs) constitute a distinctive group of membrane-bound MMPs that are central mediators of surface proteolytic events that regulate tumor cell motility, metastasis and angiogenesis. As membrane-tethered proteases, the MT-MMPs exhibit unique regulatory mechanisms and interactions with metalloproteinase inhibitors and other relevant molecules. This review will focus on new emerging information on the mechanisms that regulate MT-MMP processing, activity and inhibition, and their significance for enzyme function in the tumor microenvironment.