The ability of herpes simplex virus (HSV) to establish a lifelong, latent infection within neurons has led to much interest in the development of HSV-based vectors for neuronal gene delivery. This review discusses the progress made towards the construction of safe, replication-disabled HSV vectors that are capable of directing long-term transgene expression in latently infected neurons. Such vectors are now being investigated in a variety of animal model systems, with a view to developing gene therapy approaches to a number of metabolic and degenerative neurological diseases.