Spermatogonial stem cells (SSCs) have unique characteristics in that they produce sperm that transmit genetic information from generation to generation and they can be reprogrammed spontaneously to form embryonic stem (ES)-like cells to acquire pluripotency. In rodents, it is generally believed that the A-single (As) is the stem cell population, whereas the A-paired (Apr) and A-aligned (Aal) represent the progenitor spermatogonial population. The A1 to A4 cells, intermediate, and type B spermatogonia are considered differentiated spermatogonia. In human, very little information is available about SSCs, except for the earlier work of Clermont and colleagues who demonstrated that there are two different types of A spermatogonia, the Adark and Apale spermatogonia. The Adark spermatogonia were referred to as the reserve stem cells, whereas the Apale were considered the renewing stem cells. In this review, we outline several spermatogonial renewal schemes for both rodents and primates, including man. We also compare phenotypic markers for spermatogonia/spermatogonial stem cells in rodents and humans and address SSC potential and therapeutic application. Birth Defects Research (Part C) 87:27–34, 2009. © 2009 Wiley-Liss, Inc.