Most viruses are naturally immunogenic and can be engineered to express tumor antigen transgenes. Moreover, many types of recombinant viruses have been shown to infect professional antigen-presenting cells, specifically dendritic cells, and express their transgenes. This enhanced presentation of tumor antigens to the immune system has led to an increase in the frequency and avidity of cytotoxic T lymphocytes that target tumor cells expressing the tumor antigen(s) encoded in the vaccine vector. Logistically, recombinant viruses can be produced, administered, and quality controlled more easily compared with other immunotherapy strategies. The intrinsic properties of each virus have distinct advantages and disadvantages, which can determine their applicability in a particular therapeutic setting. The disadvantage of some vectors is the development of host-induced neutralizing antibodies to the vector itself, thus limiting its continued use. The "off-the-shelf" nature of viral vaccine platforms renders them exceptionally suitable for multicenter randomized trials. This review described and discussed the strategies used and results using viral-based vaccines, with emphasis on phases II and III clinical trials. Future directions will involve the evaluation of viral-based vaccines in the adjuvant and neoadjuvant settings, in patients with low burden metastatic disease, and in combination with other forms of therapy including immunotherapy.