The chapter discusses the current concepts and future directions in bone regeneration, a complex physiological process that occurs during fracture healing and continuous remodeling throughout adult life. It highlights the clinical conditions requiring significant bone regeneration, such as large bone defects from trauma, infection, tumor resection, and skeletal abnormalities, as well as conditions where the regenerative process is compromised, like avascular necrosis and osteoporosis. Various strategies to enhance bone regeneration are reviewed, including autologous bone grafts, free fibula vascularized grafts, allograft implants, growth factors, osteoconductive scaffolds, osteoprogenitor cells, and distraction osteogenesis. The limitations of current methods, such as the need for large bone grafts and the potential for complications, are also discussed. The chapter explores advancements in tissue engineering, gene therapy, and systemic enhancement of bone regeneration, emphasizing the ongoing research and potential for novel treatments to overcome current challenges.The chapter discusses the current concepts and future directions in bone regeneration, a complex physiological process that occurs during fracture healing and continuous remodeling throughout adult life. It highlights the clinical conditions requiring significant bone regeneration, such as large bone defects from trauma, infection, tumor resection, and skeletal abnormalities, as well as conditions where the regenerative process is compromised, like avascular necrosis and osteoporosis. Various strategies to enhance bone regeneration are reviewed, including autologous bone grafts, free fibula vascularized grafts, allograft implants, growth factors, osteoconductive scaffolds, osteoprogenitor cells, and distraction osteogenesis. The limitations of current methods, such as the need for large bone grafts and the potential for complications, are also discussed. The chapter explores advancements in tissue engineering, gene therapy, and systemic enhancement of bone regeneration, emphasizing the ongoing research and potential for novel treatments to overcome current challenges.