The notion that integration of cutting-edge technologies in stem cell research would be enhanced by proteomic analyses has emanated from rapid advances in proteome technology. These advances have increased the probability that basic properties of stem cells will be elucidated more effectively, leading to acceleration toward novel stem cell therapies. We have therefore sought to establish a world-wide alliance of proteomics and stem cell researchers, which has resulted in the foundation of an initiative supported by the Human Proteome Organisation (HUPO) and the International Society for Stem Cell Research (ISSCR) called the Proteome Biology of Stem Cells Initiative. Here we report on the rationale and goals of this initiative.