Bone tissue possesses a unique regeneration ability, translating mechanical and metabolic stimuli into a biological response. The perpetual regeneration processes allow continuous self-renewal and adaptation to prevailing mechanical forces. The complex regulation of osteoblastic differentiation during fracture repair has not been completely defined. Two different transcription factors - RUNX2 and SP7 - are considered to be master genes of osteoblastic differentiation. Furthermore, the canonical WNT pathway plays an essential role in the activation of osteoblastic differentiation during both bone growth and fracture healing. Studies of fracture healing have revealed that downregulation of the WNT pathway causes a significant reduction in new bone formation. Moreover, correct WNT signalling is also required for BMP2-induced bone formation. There is increasing evidence that patients who develop recalcitrant fracture nonunions exhibit not only reduced numbers and differentiation capacity of osteogenic progenitors but also a significant downregulation of numerous factors in the WNT pathway. Therefore, better understanding of the WNT regulatory mechanisms could reveal new strategies for the treatment of delayed fracture healing and for the tissue engineering of bone.