Oncolytic virotherapy is a kind of antitumor therapy using viruses with natural or engineered tumor-selective replication to intentionally infect and kill tumor cells. An early clinical trial has been performed in the 1950s using wild-type and non-engineered in vitro-passaged virus strains and vaccine strains (first generation oncolytic viruses). Because of the advances in biotechnology and virology, the field of virotherapy has rapidly evolved over the past two decades and innovative recombinant selectivity-enhanced viruses (second generation oncolytic viruses). Nowadays, therapeutic transgene-delivering "armed" oncolytic viruses (third generation oncolytic viruses) have been engineered using many kinds of viruses. In this chapter, the history, mechanisms, rationality, and advantages of oncolytic virotherapy by herpes simplex virus (HSV) are mentioned. Past and ongoing clinical trials by oncolytic HSVs (G207, HSV1716, NV1020, HF10, Talimogene laherparepvec (T-VEC, OncoVEX)) are also summarized. Finally, the way of enhancement of oncolytic virotherapy by gene modification or combination therapy with radiation, chemotherapy, or immune checkpoint inhibitors are discussed.