Assisted reproductive technologies (ART) have revolutionized the treatment of infertility. However, many types of infertility may still not be addressable by ART. With recent successes in identifying many of the genetic factors responsible for male infertility and the future prospect of whole individual human genome sequencing to identify disease causing genes, the possible use of gene therapy for treating infertility deserves serious consideration. Gene therapy in the sperm and testis offers both opportunities and obstacles. The opportunities stem from the fact that numerous different approaches have been developed for introducing transgenes into the sperm and testis, mainly because of the interest in using sperm mediated gene transfer and testis mediated gene transfer as ways to generate transgenic animals. The obstacles arise from the fact that it may be very difficult to carry out gene therapy of the testis and sperm without also affecting the germline. Here we consider new developments in both sperm and testis mediated gene transfer, including the use of viral vectors, as well as the technical and ethical challenges facing those who would seek to use these approaches for gene therapy as a way to treat male infertility.