As a hard-to-treat complicated condition, cancer was treated through the surgical removal techniques before the early twentieth century. Thereafter, a combination of surgical removal and chemotherapy, radiotherapy, and immunotherapy served this purpose. In addition, virotherapy was born of the advances in molecular biology and genetics. Improved tumorspecificity, targeted delivery, and increased efficiency have been the fruits of the genetic modifications of oncolytic viruses, which have resulted in the development of new weapons against cancer, especially for patients with cancerous inoperable tumors. This paper presents a review of the basis for oncolytic virotherapy and development of the genetically modified tumor-specific viruses. A discussion on the contribution of oncolytic virotherapy to the treatment of cancer, clinical trials and the success of rate of these trials is also presented. The conclusion section addresses the safety concerns articulated through the previous trials and the current and future challenges to oncolyticvirotherapy.