The study of herpes virus biology has produced two vector delivery strategies which exploit the highly evolved neuronal tropism and life cycle regulation exhibited by this class of viruses. Amplicon and recombinant herpes simplex virus systems show promise for use in gene transfer to the nervous system and although neither vector has been used in clinical trials to date, their application to gene delivery and perturbation of neuronal physiology have been well established. We will review the properties of the herpes amplicon system, and demonstrate its utility in neuroscience applications.