The matrix metalloproteinase (MMP) family of extracellular proteinases regulates development and physiologic events. Genetic analyses using transgenic mice that have gain and loss of function of MMPs or of their endogenous inhibitors, the TIMPs, and pharmacogenetic studies with chemical inhibitors have begun to elucidate the roles that they play. It is now clear that these enzymes are important for cell migration, invasion, proliferation, and apoptosis. They regulate many developmental processes, including branching morphogenesis, angiogenesis, wound healing, and extracellular matrix degradation. The matrix metalloproteinases (MMPs) are a family of extracellular matrix (ECM)-degrading enzymes that shares common functional domains and activation mechanisms (Sternlicht et al. 2000). These are Ca2+-and Zn2+-dependent endopeptidases that are active at neutral pH. They are synthesized as secreted or transmembrane proenzymes and processed to an active form by the removal of an amino-terminal propeptide. The propeptide is thought to keep the enzyme in latent form by the interaction of a cysteine residue in this peptide with the zinc moiety in the enzyme active site. Disruption of this interaction triggers the cysteine switch mechanism and results in activation of the enzyme. MMPs can be activated by chaotropic agents or by cleavage of the propeptide by members of the MMP family or by other proteases. They are inhibited by a family of tissue inhibitors of metalloproteinases, the TIMPs. As a family, MMPs degrade most components of the ECM. There are now> 20 members of the MMP family. There are several distinct subgroups based on preferential substrates or similar structural domains: Collagenases that are active against fibrillar collagen, gelatinases that have high activity against denatured collagens, stromelysins that degrade noncollagen components of the ECM, membranetype MMPs (MT-MMPs) that are transmembrane molecules, and other less characterized members (Fig. 1; Table 1).