Fracture nonunion, delayed union, and osteomyelitis remain serious problems with substantial morbidity and mortality rates. Healing promoters, including bone morphogenic proteins, fibroblast growth factors, and transforming growth factor–β, regulate bone growth in experimental models, such as those employing a “critical gap” to establish nonunion, but have not been effective in clinical situations. This paradox may relate to the fact that such agents target cells, yet in the setting of a clinical nonunion or osteomyelitis, the affected area is frequently hypovascular and therefore deficient in target precursor cells. Wound healing is dependent on local tissue vascularity. Surgical procedures, such as local and remote tissue transfer, which are designed to modify this cell-deficient, poorly vascularized environment, have proved very successful but are often complex and costly. No simple pharmacologic means of upregulating such angiogenesis currently exists.