The oncolytic virus (OV) field has entered an exciting period in its evolution in which our basic understanding of viral biology and anti-cancer potential are being actively translated into viable therapeutic options for aggressive malignancies. OVs are naturally occurring or engineered viruses that are able to exploit cancer-specific changes in cellular signaling to specifically target cancers and their microenvironment. The direct cytolytic effect of OVs on cancer cells is known to release antigens, which can begin a cascade of events that results in the induction of anti-cancer adaptive immunity. This response is now regarded as the most critical mechanism of OV action and harnessing it can lead to the elimination of distant micrometastases as well as provide long-term anti-cancer immune surveillance. In this review, we highlight the development of the OV field, why OVs are gaining an increasingly elevated standing as members of the cancer immunotherapy armamentarium, and finally, ongoing clinical studies that are aimed at translating unique OV therapies into approved therapies for aggressive cancers.