Cutaneous wound healing is a complex tissue response that requires a coordinated interplay of multiple cells in orchestrated biological processes to finally re-establish the skin’s barrier function upon injury. Proteolytic enzymes and in particular matrix metalloproteinases (MMPs) contribute to all phases of the healing process by regulating immune cell influx, facilitating migration of fibroblasts and keratinocytes, and remodeling of the scar tissue. As a result of these pleiotropic functions in the healing skin wound, uncontrolled activities of MMPs are associated with impaired wound healing, a growing health problem in Western countries due to increased life expectancies and rising rates of underlying diseases, such as diabetes. However, detailed mechanisms have been only partially unraveled, and new diagnostic tools and more targeted therapies are urgently needed. In this review, we discuss the roles of MMPs in acute and chronic wound healing and summarize current therapeutic approaches aiming at inhibiting aberrant MMP activities in healing disorders.