Viruses that replicate in and kill tumor cells have attracted attention as a new modality for cancer treatment, i.e., oncolytic virotherapy. Clinical trials using some of these potent viruses are currently under way. The fundamental principle of using replication-competent viruses for cancer treatment is that the viruses replicate in permissive tumor cells, spread to neighboring tumor cells, and exterminate all tumor cells, overcoming the delivery efficiency shortfall of traditional gene therapy. Compared to other viruses, HSV is advantageous in that it is well understood, infects a broad range of host cells, rapidly and effectively lyses cells, is easily manipulated genetically, and has an established antiviral therapy. Most replication-competent HSVs that have been investigated for safety and efficacy in cancer therapy are based on the manipulation of one or a few accessory genes. In this paper, we review the current status of oncolytic virotherapy using replication-competent HSV and introduce a novel, spontaneously attenuated HSV, designated HF10, which shows safe and satisfactory anti-cancer effects in animals and humans.