Stem cells have the capacity both to self‐renew and to give rise to differentiated progeny, and are vital to the organization of multicellular organisms. Stem cells raise a number of fundamental questions regarding lineage restriction and cellular differentiation, and they hold enormous promise for cell‐based therapies. Here I propose a theoretical framework for stem cell biology based on the concepts of autopoiesis (self‐production) and complementarity. I argue that stem cells are pivotal in the self‐production of the organism and that we (...) need complementary approaches to understand their probabilistic behavior. I discuss how this framework generates testable hypotheses regarding stem‐cell functions. BioEssays 26:1013‐1016, 2004. © 2004 Wiley Periodicals, Inc. (shrink)