Matrix metalloproteinases (MMPs) degrade all protein components of the extracellular matrix. Functionally, they contribute to several different physiologic conditions, such as angiogenesis or bone remodeling, as well as pathologic conditions in humans, such as rheumatoid arthritis and tumor growth. MMPs seem to be important in the pathogenesis of inflammatory demyelinating diseases of the central and peripheral nervous system, especially in MS and in Guillain-Barré syndrome (GBS). Key mechanisms in the genesis of inflammatory demyelination, such as leukocyte recruitment, blood-brain barrier or blood-nerve barrier breakdown, myelin destruction, and release of disease-promoting cytokines, are considered to be MMP-dependent processes. In experimental autoimmune encephalomyelitis, an animal model of MS, and experimental autoimmune neuritis, an animal model of GBS, different synthetic inhibitors targeting MMP activity are able to suppress and even reverse ongoing disease. This evidence points to MMPs as new targets for treatment in inflammatory demyelination.