Spermatogenesis is a complex developmental process that ultimately generates mature spermatozoa. This process involves a phase of proliferative expansion, meiosis, and cytodifferentiation. Mouse models have been widely used to study spermatogenesis and have revealed many genes and molecular mechanisms that are crucial in this process. Although meiosis is generally considered as the most crucial phase of spermatogenesis, mouse models have shown that pre-meiotic and post-meiotic phases are equally important. Using knowledge generated from mouse models and in vitro studies, the current review provides an overview of the molecular control of rodent spermatogenesis. Finally, we briefly relate this knowledge to fertility problems in humans and discuss implications for future research. This article is part of a Special Issue entitled: Molecular Genetics of Human Reproductive Failure.