Genetically modified herpes simplex viruses (HSVs) have been exploited for both antitumor therapy and vaccine delivery. These mutant viruses retain their ability to replicate and lyse permissive cells, including many tumor types, and are referred to as oncolytic HSVs. In addition, deletion of nonessential genes permits the introduction of foreign genes to augment the antitumor effect by either immune stimulation, targeting for select tumors, or expression of tumor or vaccine antigens. This article reviews the development of oncolytic HSVs as an anticancer therapy, as well as the application of HSV-1 vectors for delivery of targeted antigens or as vaccine adjuvants. The impact of these novel vectors with respect to enhanced antitumor activity and development of antitumor vaccination strategies is discussed. © 2011 Future Medicine Ltd.