The use of replication-competent viruses that can selectively replicate in and destroy neoplastic cells is an attractive strategy for treating cancer. Various oncolytic viruses have been taken to clinical trials since a recombinant virus was first applied to cancer patients a decade ago. The concept of the therapy is simple: infectious virus kills the host cancer cells in the course of viral replication. It is important, however, that the virus does not harm the surrounding normal tissue. Oncolytic viruses can be classified largely into two groups: DNA viruses genetically engineered to achieve cancer specificity (e.g. adenovirus, herpes simplex virus and vaccinia) and RNA viruses of which human is not the natural host (e.g. Newcastle disease virus and reovirus). Prostate cancer has always been one of the major targets of oncolytic virus therapy development. The result of six clinical trials for prostate cancer has been published and several trials are now going on. Forty-eight of 83 (58%) patients evaluated in the phase I studies demonstrated a >25% decrease in serum prostate-specific antigen level without evidence of severe toxicities. The result shows the oncolytic virus therapy is promising toward clinical application. Here, we review the recent advances in the field and summarize the results from clinical trials.