Many types of oncolytic viruses, wild-type virus, attenuated viruses and genetically-modified viruses, have been developed as an innovative cancer therapy. The strategies, nature, and technologies of oncolytic virus products are different from the conventional gene therapy products or cancer therapy products. From the regulatory aspects to ensure the safety, efficacy and quality of oncolytic viruses, there are several major points during the development, manufacturing, characterization, non-clinical study and clinical study of oncolytic viruses. The major issues include 1) virus design (wild-type, attenuated, and genetically engineered strains), 2) poof of concept in development of oncolytic virus products, 3) selectivity of oncolytic virus replication and targeting to cancer cells, 4) relevant animal models in non-clinical studies, 5) clinical safety, 6) evaluation of virus shedding. Until now, the accumulation of the information about oncolytic viruses is not enough, it may require the unique approach to ensure the safety and the development of new technology to characterize oncolytic viruses.