Growth factors and their underlying signaling pathways play an integral part in the regulation of cellular processes in cranio-maxillofacial (CMF) tissue engineering. The transforming growth factor-β (TGF-β) family, bone morphogenetic proteins (BMPs), vascular endothelial growth factor (VEGF), fibroblast growth factors (FGFs), platelet-derived endothelial growth factors (PDGFs), parathyroid hormone (PTH), and insulin-like growth factor (IGF) are among growth factors that play a significant role in the process of bone and tissue regeneration. TGF-β and BMPs are particularly important in regulating bone formation and regeneration. VEGF, FGFs, and PDGFs promote cell proliferation, migration, angiogenesis, and soft tissue repair. PTH is responsible for regulating calcium homeostasis and promoting bone formation, while IGF regulates cell proliferation, differentiation, and survival. Understanding the underlying mechanisms of these signaling pathways can pave the way for development of novel therapeutic approaches in CMF tissue engineering. This, in turn, offers promise for individuals affected by craniofacial defects resulting from congenital malformations, traumatic incidents, or cancer. This chapter aims to provide a brief historical overview and fundamental concepts associated with these signaling pathways and growth factors in bone and CMF tissue engineering.