Viral vectors have been frequently applied for cancer therapy including adenoviruses, adeno-associated viruses, herpes simplex viruses, retroviruses, lentiviruses, alphaviruses, flaviviruses, measles viruses, rhabdoviruses, vaccinia viruses, Newcastle disease viruses, poxviruses, coxsackieviruses, reoviruses, and polyoma viruses. Viral vector-based cancer therapy has included delivery of anti-tumor, toxic, and suicide genes, tumor-associated antigens (TAAs), and immunostimulatory genes. Attenuated and oncolytic viruses, either engineered or naturally occurring, have played an important role in cancer therapy. Numerous studies in various animal models have demonstrated immune responses against TAAs and protection against tumor challenges. Moreover, tumor regression and eradication and cure have been achieved in animals with preexisting tumors. Clinical trials have also showed safety and efficacy. The adenovirus-based drug Gendicine® has been approved for non-small cell lung cancer, Oncorine® for nasopharyngeal carcinoma, the herpes simplex virus-based T-VEC drug for the treatment of melanoma, and reovirus-based Reolysin for ovarian and pancreatic cancer and malignant glioma.