Adult stem cells persist lifelong in the organism, where they are responsible for tissue homeostasis and repair. It is commonly assumed that their maintenance and function are facilitated in local environments called "stem cell niches." Although there is convincing evidence that a variety of niche components determine stem cell fate, the regulatory details of stem cell-niche interactions are widely unknown. To pave the way for a substantiated discussion of these interactions, we first focus on the stem cells themselves and describe the stem cell defining criteria and their implications. The fate of the cells that fulfill these criteria is regulated by a broad spectrum of factors and regulatory mechanisms. A summary of established components and their action is given exemplary for the hematopoietic system. The complexity resulting from the interplay of various cell types, signaling molecules, and extracellular structures can be boiled down to important key features as exemplified by the presented model of hematopoietic stem cell organization. Although neglecting many details, we show that this and similar models have the power to yield intriguing results as proven by the agreement of the presented model with experimental data and the predictions derived from model simulations. Finally, we will discuss the paradigm of systems biology and give a summary of the techniques that promise to unveil further details of the organization principles of stem cell niches at different levels. The synergistic effect of the described techniques together with the integration of their results into a unified model that allows quantitative evaluation and predictions may lead to a better and more systematic understanding of the most relevant niche elements and their interactions.