Matrix metalloproteinases (MMPs) have been implicated in various nervous system diseases, including multiple sclerosis (MS), malignant gliomas, stroke, Alzheimer's disease, and viral infections of the central nervous system (CNS). MMPs are involved in the regulation of cell function, extracellular matrix (ECM) remodeling, survival, angiogenesis, inflammation, and signaling. They can degrade all constituents of the ECM, leading to pathological conditions such as cancer metastasis. In the nervous system, MMPs are associated with pathogenesis, particularly in MS and malignant gliomas. They contribute to neuropathology by facilitating leukocyte entry into the CNS, disrupting the blood-brain barrier (BBB), perpetuating inflammatory responses, and causing demyelination and neuronal death. MMPs can also have beneficial functions during neural development and repair after brain injury, such as regulating axonal growth and facilitating precursor cell migration. The ADAM family of metalloproteinases, which shares some properties with MMPs, may also play a role in CNS pathophysiology. The challenges in understanding the roles of MMPs in the CNS include defining the balance between beneficial and detrimental effects, identifying specific substrates, and developing more specific inhibitors. Despite these challenges, the use of MMP inhibitors to treat CNS diseases is warranted, especially when inflammation is a key factor in disease progression.Matrix metalloproteinases (MMPs) have been implicated in various nervous system diseases, including multiple sclerosis (MS), malignant gliomas, stroke, Alzheimer's disease, and viral infections of the central nervous system (CNS). MMPs are involved in the regulation of cell function, extracellular matrix (ECM) remodeling, survival, angiogenesis, inflammation, and signaling. They can degrade all constituents of the ECM, leading to pathological conditions such as cancer metastasis. In the nervous system, MMPs are associated with pathogenesis, particularly in MS and malignant gliomas. They contribute to neuropathology by facilitating leukocyte entry into the CNS, disrupting the blood-brain barrier (BBB), perpetuating inflammatory responses, and causing demyelination and neuronal death. MMPs can also have beneficial functions during neural development and repair after brain injury, such as regulating axonal growth and facilitating precursor cell migration. The ADAM family of metalloproteinases, which shares some properties with MMPs, may also play a role in CNS pathophysiology. The challenges in understanding the roles of MMPs in the CNS include defining the balance between beneficial and detrimental effects, identifying specific substrates, and developing more specific inhibitors. Despite these challenges, the use of MMP inhibitors to treat CNS diseases is warranted, especially when inflammation is a key factor in disease progression.