The idea of using the lytic power of viruses against malignant cells has been entertained for many decades. However, oncolytic viruses gained broad attention as an emerging anti-cancer therapy only recently with the successful implementation of several oncolytic viruses to treat advanced melanoma. Here we review the history of oncolytic viruses in the Russian Federation and recent biotechnological advances in connection with the perspectives of their practical use against aggressive tumors such as glioblastoma or pancreatic cancer. A particular emphasis is made on novel applications of safe non-lytic virus-derived vectors armed with prodrug-converting enzyme transgenes. Rational improvement of oncotropism by conjugation with biopolymers and nanoformulations is also discussed.