Germline stem cells (GSCs), which can self-renew and generate differentiated progeny, are unique stem cells in that they are solely dedicated to reproduction and transmit genetic information from generation to generation. Through the use of genetic techniques in Drosophila, Caenorhabditis elegans, and mouse, exciting progress has been made in understanding molecular mechanisms underlying interactions between stem cells and niches. The knowledge gained from studying GSCs has provided an intellectual framework for defining niches and molecular regulatory mechanisms for other adult stem cells. In this review, we summarize recent progress and discuss conserved mechanisms underlying GSC self-renewal and differentiation by comparing three GSC systems. Because GSCs and other adult stem cells share "stemness," we hope this review will help define fundamental principles of stem cell regulation and provide further guidance for future studies of other adult stem cells.