Members of the family of matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of inflammatory demyelination. MMPs apparently mediate important steps in the genesis of inflammatory demyelination, such as cell migration, blood-brain/nerve barrier breakdown, demyelination, and cytokine activation. This review will highlight in vitro as well as in vivo findings, which support the importance of this group of proteases in the pathogenesis of inflammatory demyelinating disorders of the central and peripheral nervous system.