The intimate connection, both physical and biochemical, between blood vessels and bone cells has long been recognized. Genetic, biochemical, and pharmacological studies have identified and characterized factors involved in the conversation between endothelial cells (EC) and osteoblasts (OB) during both bone formation and repair. The long-awaited FDA approval of two growth factors, BMP-2 and OP-1, with angiogenic and osteogenic activity confirms the importance of these two processes in human skeletal healing. In this review, the role of osteogenic factors in the adaptive response and interactive function of OB and EC during the multi-step process of bone repair will be discussed.