Stem cells have tremendous therapeutic potential for a series of pathologies ranging from cancer to genetic diseases. The obstacles to exploiting their potential reside mainly in their limited numbers or potency. Prostaglandins are known to be involved in many physiological and pathological processes. Among these, their importance in stem cell development is just starting to emerge. The recent findings by North and colleagues (Nature, 2007; 447:1007-1011) uncover a crucial role for PGE2 in hematopoietic stem cell growth and development not only in embryonic, but also in adult stem cell homeostasis in both simple and complex vertebrate systems. This new information adds to recent advances in the study of PGE2's role in many diseases and in the reaction to various cellular stress conditions. This is the perfect time to improve our knowledge of stem cell regulation, which hopefully will lead to improved stem cell-based therapeutic options and also to better understand and manage current anti-inflammatory and immuno-suppressive drugs in the therapy of cancer and other diseases.