This overview describes the considerations involved in the preparation and use of herpes simplex virus type 1 (HSV-1) as a vector for gene transfer into neurons. Strategies for gene delivery into neurons, either to study the molecular biology of brain function or for gene therapy, must utilize vectors that persist stably in postmitotic cells and that can be targeted both spatially and temporally in the nervous system in vivo. This unit describes the biology of HSV-1 along with a discussion covering development of amplicon and genomic HSV-1 vectors. Advantages and disadvantages of current HSV-1 vectors are presented, and HSV-1 vectors are compared with other vectors for gene transfer into neurons.