The use of oncolytic herpes simplex virus type 1 (HSV-1) is a promising strategy for cancer treatment. Accumulating evidence indicates that, aside from the extent of replication capability within the tumor, the efficacy of an oncolytic HSV-1 depends on the extent of induction of host antitumor immune responses. Ways to modify the host immune responses toward viral oncolysis include expression of immunostimulatory molecules using oncolytic HSV-1 as a vector and co-administration of reagents that modulate immune reactions. Viral propagation may be enhanced via temporary suppression of innate immune responses. Elucidation of the role of the host immune system in oncolytic HSV-1 therapy is the key to establishing the approach as a useful clinical means for cancer treatment.