Colorectal cancer is the third most common neoplasm in the world and the third leading cause of cancer-related deaths in the USA. A safer and more effective therapeutic intervention against this malignant carcinoma is called for given the limitations and toxicities associated with the currently available treatment modalities. Immuno-oncolytic or oncolytic virotherapy, the use of viruses to selectively or preferentially kill cancer cells, has emerged as a potential anticancer treatment modality. Oncolytic viruses act as double-edged swords against the tumors through the direct cytolysis of cancer cells and the induction of antitumor immunity. A number of such viruses have been tested against colorectal cancer, in both preclinical and clinical settings, and many have produced promising results. Oncolytic virotherapy has also shown synergistic antitumor efficacy in combination with conventional treatment regimens. In this review, we describe the status of this therapeutic approach against colorectal cancer at both preclinical and clinical levels. Successes with and the challenges of using oncolytic viruses, both as monotherapy and in combination therapy, are also highlighted.