The production of functional spermatozoa is a complex process requiring the coordinated expression of thousands of genes. It is likely that the intricate nature of these interactions contributes to the large number of idiopathic male infertility cases seen in humans. Conversely, the complexity of the highly regulated and interconnected processes of spermatogenesis and posttesticular sperm maturation events offers opportunities for the development of male-based contraceptive targets. The recent advances in genetic manipulation technologies and the completion of the human and mouse genome sequencing programs have provided scientists with sophisticated ways to generate mouse models for the study of basic biological mechanisms, in order to understand disease pathology and develop novel therapeutic approaches. The three common types of mouse model used for medical research are transgenic, knockout/knockin, and chemical-induced point mutant mice. Each type has relative strengths and weaknesses with respect to its fidelity to the disease processes in humans. In this chapter, we focus on the utility of the different types of mouse model in obtaining a better understanding of the mechanisms that control spermatogenesis and developing male-based contraceptive regimens.