Blood-brain barrier (BBB) leakage and brain edema is a critical part of stroke pathophysiology. In this mini-review, we briefly survey the potential role of matrix metalloproteinases (MMPs) in BBB dysfunction. A large body of data in both experimental models as well as clinical patient populations suggests that MMPs may disrupt BBB permeability and interfere with cell-cell signaling in the neurovascular unit. Hence, ongoing efforts are underway to validate MMPs as potential biomarkers in stroke as well as pursue MMP blockers as therapeutic opportunities. Because BBB perturbations may also occur in neurodegeneration, MMPs and associated neurovascular unit mechanisms may also be potential targets in a broader range of CNS disorders.