Viral vectors have frequently been applied in gene therapy with the final goal of treating various diseases in the areas of neurology, neurodegeneration, metabolic disease, and cancer. Vectors have been engineered based on AAV, adenoviruses, alphaviruses, herpes simplex viruses, lentiviruses, and retroviruses. Some vectors are suitable for short-term episomal transgene expression, whereas others are integrated into the host cell genome to provide long-term expression. Additionally, hybrid vectors with favorable features from different viruses have been developed. Therapeutic genes of choice have typically been toxic genes such as thymidine kinase, pro-apoptotic genes like Bax, and immunostimulatory genes (for instance, interleukin-12). A large number of animal studies have demonstrated proof of concept of viral gene therapy. Many types of viral vectors have been employed in more than 700 clinical trials that have been carried out or are currently in progress.