It was first reported in 1994, that transplantation of germ cells from fertile donor mice to the testes of infertile recipient mice can result in donorderived spermatogenesis and transmission of the donor haplotype to offspring of recipient animals. More recently, germ cell transplantation was successfully performed also in large animals. Importantly, germ cell transplantation was successful between unrelated, immuno-competent large animals, whereas efficient donor-derived spermatogenesis in rodents requires syngeneic or immuno-compromised recipients. Efficiency of colonization of the recipient testis by donor-derived germ cells can be improved by pretreatment of the recipient animal to deplete endogenous germ cells. Genetic manipulation of isolated germ line stem cells and subsequent transplantation will result in production of transgenic sperm. Transgenesis through the male germ line has tremendous potential in domestic animal species where embryonic stem cell technology is not available and current options to generate transgenic animals are inefficient. Introduction of a genetic change prior to fertilization will circumvent problems associated with manipulation of early embryos and developmental abnormalities associated with somatic cell nuclear transfer and reprogramming. It is expected that germ cell transplantation will provide a viable alternate approach to generate germ line transgenic domestic animals. As an alternative to transplantation of isolated germ cells to a recipient testis, ectopic grafting of testis tissue from diverse mammalian donor species, including primates, into a mouse host represents a model to study spermatogenesis, to investigate the effects of substances with the potential to affect male fertility, and to produce fertile sperm from immature donors. Therefore, transplantation of germ cells or testis tissue are uniquely valuable approaches for the study, preservation and manipulation of male fertility in mammalian species.