This chapter reviews the scientific basis for the use of these vectors for foreign gene delivery to the adult nervous system, the work done in vivo in animal models, and the types of human diseases that are potential targets for this form of somatic gene therapy. Herpes and adenovirus are the only successful means to date by which foreign genes have been introduced into postmitotic neurons in the adult animal. Neurons are an extremely important cell target for somatic gene therapy in neurological disorders of the central nervous system, but are difficult to manipulate genetically in the adult, since they do not divide postnatally and cell division is a prerequisite for gene delivery in most experimental procedures. Two basic types of Herpes Simplex Virus (HSV) vectors have been used for gene transfer: plasmid-derived vectors, termed amplicons, and recombinant virus vectors.