Osteoblasts are an important cellular component of the bone microenvironment controlling bone formation and hematopoiesis. Understanding the cellular and molecular mechanisms by which osteoblasts regulate these processes is a rapidly growing area of research given the important implications for bone therapy, regenerative medicine, and hematopoietic stem cell transplantation. Here we summarize our current knowledge regarding the cellular and molecular crosstalk driving bone formation and hematopoiesis and will discuss the implications of a recent finding demonstrating that osteoblasts are a cellular source of erythropoietin .