Abstract: The specialty of craniofacial surgery is broad and includes trauma, aesthetics, reconstruction of congenital deformities, and regeneration of tissues. Moreover, craniofacial surgery deals with a diverse range of tissues including both “soft” and “hard” tissues. Technological advances in materials and biological sciences and improved surgical techniques have remarkably improved clinical outcomes. The quest to raise the bar for patient care continues to inspire advances for predictable biological regeneration of soft and hard tissues. As a consequence of this quest for advancement, a wide spectrum of biologicals is becoming available to surgeons. Is the use of recombinant DNA engineered biologicals daring? Sensible? Logical? Timely? Safe? It is crucial for the practicing craniofacial surgeon to take a step back periodically and carefully review the biological factors that have the potential for dramatically altering the discipline of craniofacial surgery. With this emphasis, the coauthors of this article will focus on growth factor technology underscoring bone tissue regeneration. As the 21st-century matures, recombinant human biologicals will have an overwhelming impact on the practice of craniofacial surgery.