The progression of spermatogenesis relies on the precise regulation of spermatogonial self-renewal and differentiation. Many genes/proteins have been identified with specific expression profiles in individual spermatogonial cell types but the molecular mechanism of their regulation is still obscure. In this review, an overview of current knowledge on the various factors essential for these two major steps of spermatogonial development is presented. Elucidating the function of these factors was typically made possible through either naturally occurring mutant mice or genetically modified mice, in which a specific and clearly defined spermatogonial arrest is seen. In addition, a few factors, which are potentially important but less clearly defined, are also included. Moreover, the relevance and postulated interactions between these factors is discussed.