Germline stem cells (GSCs) are the self-renewing population of germ cells that serve as the source for gametogenesis. GSCs exist in diverse forms, from those that undergo strict self-renewing asymmetric divisions in Drosophila to those that maintain their population by balancing between mitosis and differentiation in Caenorhabditis elegans. Most vertebrate spermatogonial GSCs appear to adopt an intermediate strategy. In most animals, GSCs are established during preadult gonadogenesis following the proliferation and migration of embryonic primordial germ cells. GSCs produce numerous gametes throughout the sexually active period of adult life. The establishment and self-renewing division of GSCs are controlled by extracellular signals such as hormones from the hypothalamic-pituitary axis and local interactions between GSCs and their neighboring cells. These extracellular signals may then influence differential gene expression, cell cycle machinery, and cytoskeletal organization of GSCs for their formation and/or divisional asymmetry. In addition, the GSC mechanism is related to that for germline and sex determination. Current knowledge has provided a solid framework for further study of GSCs and stem cells in general.