Tissue-specific stem cells are uncovered in a growing number of organs by their molecular expression profile and their potential for self-renewal, multipotent differentiation and tissue regeneration. Whether the pituitary gland also contains a pool of versatile 'master' cells that drive homeostatic, plastic and regenerative cell ontogenesis is at present unknown. Here, I will give an overview of data that may lend support to the existence of stem cells in the postnatal pituitary. During the many decades of pituitary research, various approaches have been used to hunt for the pituitary stem cells. Transplantation and regeneration studies advanced chromophobes as possible source of new hormonal cells. Clonogenicity approaches identified pituitary cells that clonally expand to floating spheres, or to colonies in adherent cell cultures. Behavioural characteristics and changes of marginal, follicular and folliculostellate cells during defined developmental and ( patho-)physiological conditions have been interpreted as indicative of a stem cell role. Expression of potential stem cell markers like nestin, as well as topographical localization in the marginal zone around the cleft has also been considered to designate pituitary stem cells. Finally, a 'side population' was recently identified in the postnatal pituitary which in many other tissues represents a stem cell-enriched fraction. Taken together, in the course of the long-standing study of the pituitary, several arguments have been presented to support the existence of stem cells, and multiple cell types have been placed in the spotlight as possible candidates. However, none of these cells has until now unequivocally been shown to meet all quintessential characteristics of stem cells. Copyright c 2007 S. Karger AG, Basel.