Stem cells are cells that, upon division, can produce new stem cells as well as daughter cells that initiate differentiation along a specific lineage. Understanding how stem cells are regulated is crucial in learning how tissues are formed and maintained. The rapid increase in genomic information offers an ever-rising tide of information about protein structure and function. Together with the availability of the atomic coordinates of key regulatory molecules such as receptors and transcription factors, such proteomics techniques have yielded global insight in stem cell behavior. Here I will show that it is important to exploit such opportunities in concert with the more classical, problem-oriented research on stem cells and that knowledge of protein structure and function remains central to an academic understanding of essentially all areas of stem cell biology.