To form tumors successfully at sites remote from the primary tumor, metastatic cells must be endowed with particular properties. They must detach from the primary tumor and enter the blood circulation, where they must resist hemodynamic shearstress, "home" to the target organ, successfully extravasate, and then migrate through dense stroma to a site favorable for tumor growth. Recent results with genetically engineered mouse models have generated data which clearly challenge the classic dogma stating that matrix metalloproteinases (MMPs) promote metastasis solely by modulating the remodeling of extracellular matrix (ECM). Instead, it is becoming clear that MMPs and their natural inhibitors have multiple biological functions that not only challenge our view on how MMPs promote metastasis, but also raise for the first time the idea that secretion of MMPs by the host could protect it from tumor growth, at least in some types of cancer or at specific stages of tumor progression.