Gene transfer is a potential means of treating chronic neurologic disorders and injury related neural degeneration. One approach for transferring genes to the CNS is to genetically modify cells in vitro and then transplant the cells to the CNS. For example, fibroblasts can be infected with a replication-defective retrovirus expressing a transgene, and can then be transplanted into the brain or spinal cord, thereby providing neurotrophic factors and substrates for axonal growth and elongation. In this review we discuss the grafting of neurotrophic factor secreting autologous fibroblasts in the rat and primate CNS. NGF secreting grafts have been shown to prevent degeneration of cholinergic neurons in the basal forebrain of primates and to induce sprouting of sensory, motor, and noradrenergic neurites after spinal cord injury. These results suggest the potential usefulness of ex vivo gene transfer for the treatment of Alzheimer's disease and spinal cord injury.