Cancer is a complex disease and is difficult to treat. Until the early twentieth century, it was treated by surgical removal which later on was combined with chemotherapy, radiotherapy and immunotherapy. However, advances in molecular biology and genetics lead to the establishment of virotherapy. The genetic modification of oncolytic viruses has improved their tumor specificity, targeted delivery and increased efficacy, leading to the development of new weapons for the war against cancer especially in those cancer patients in which tumor is inoperable. In this review, we describe the basis of oncolyticvirotherapy and how the genetically modified tumor-specific viruses are developed. Utility of oncolytic virotherapy to treat cancer, clinical trials and their success rate are also discussed. We conclude with current and future challenges in oncolyticvirotherapy and the safety concerns raised by the trials conducted so far.