Transgenic mice have become important model systems for studying molecular, cellular, organ, and whole animal physiology. In particular, transgenic technology allows determination of cell lineage differentiation and the role(s) of specific proteins in mammalian development and oncogenesis. Transgenic mice can be created that express wild-type genes, mutant genes, marker genes or cell lethal genes in a tissue-specific manner. In addition, homologous recombination strategies in embryonic stem cells permit more sophisticated manipulation of the mammalian genome, including the functional deletion of specific genes in whole mice or in a specific tissue. Since all transgenic mice created must be bred to study the consequences of transgene or mutant allele expression, a number of effects of these genome manipulations on the reproductive development and function of these mice have been uncovered. In this review, we summarize the transgenic mouse models in which defects and abnormalities in the reproductive axis have been demonstrated.