Central nervous system malignancies - particularly glioblastoma multiforme - pose significant problems for the development of novel therapeutics. In the absence of advances with standard surgical and chemotherapeutic approaches, the utilization of genetically engineered viruses - both as direct oncolytic agents (virus therapy) and for the delivery of foreign proteins (gene therapy) - represents a significant advance in the experimental approach to the management of patients with incurable tumours. Among other viruses, herpes simplex virus (HSV) offers an opportunity to influence the replication of tumour cells directly within the central nervous system. The propensity for HSV to replicate in tumour cells, and its large coding capacity, provide an experimental model for the development of novel therapeutics. The status of these experimental approaches and Phase I studies are summarized.