The present invention provides methods and compositions for enhancing recovery in a subject suffering from damage to the nervous system. In particular, the invention includes a method for promoting recovery and / or reorganization in the nervous system of a subject in need of enhancement of recovery and / or reorganization of the nervous system as a result of ischemic, hemorrhagic, neoplastic, degenerative, or traumatic damage by focally administering a composition comprising a proteolysis-enhancing agent such as tissue plasminogen activator (tPA), plasmin, or a PAI inhibitor to the nervous system of the subject. In some embodiments an additional active agent is also administered. The composition can be delivered using a variety of techniques including injection, via infusion pump, from an implantable microchip, or using a polymeric delivery vehicle. The composition can be administered, for example, to one or more subdivisions or areas of the brain, the spinal cord, or to one or more nerves or nerve tracts innervating diverse regions of the body. The invention also includes a drug delivery device for implantation into the nervous system to promote nervous system reorganization and / or recovery following ischemic, hemorrhagic, neoplastic, traumatic or degenerative damage, the drug delivery device comprising a biocompatible polymer and a proteolysis-enhancing agent such as tissue plasminogen activator (tPA), plasmin, or a PAI inhibitor, wherein the proteolysis-enhancing agent is released from the polymer in an amount effective to promote structural reorganization of the nervous system. In some embodiments the biocompatible polymer is a hydrogel.