Amyotrophic Lateral Sclerosis (ALS) is a debilitating neurodegenerative and neurovascular disorder with multi-factorial molecular mechanisms of pathology. At the very core of B-CNS B alterations associated with ALS are the keys to barrier immunopenetration by inflammatory cells into the CNS parenchyma, the Matrix Metallo Proteinases (MMPs). MMPs are a vastly diverse family of endo peptidases that possess a multitude of CNS functions, substrates and regulatory mechanisms. This review will examine the accumulated evidence describing MMPs and TIMPs (Tissue Inhibitors of Metallo Proteinases) and discuss the various CNS processes in the neurodegenerative environment that MMPs are implicated in including neuro and systemic inflammation, cell damage and apoptosis, as well as interactions with vascular growth factors. In conclusion, opposing MMP functions and their contribution to B-CNS-B disruption in ALS will be addressed with perspective into potential future studies.