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Tissue engineering emerged as an interdisciplinary field to address organ/tissue transplantation limitations. Besides an appropriate scaffold and cell source, growth factors (GFs) represent attractive tools and key actors in tissue engineering/regeneration. Mitogenic, angiogenic, chemotactic, or osteoinductive, delivering GFs is crucial for mediating the interaction cells/tissues and biomaterials in view of an effective regeneration of functional tissues. Since bone implants are the second most frequent tissue transplanted worldwide, we provide herein insights into the potential use of GFs in bone tissue engineering, their multiple delivery approaches, and their in vitro/in vivo effects on cells/tissues behavior. From bench to bedside, we discuss the clinical use of cell/GFs functionalized materials to repair bone defects. The “good” but also the “ugly face” of GFs are highlighted in order to guide future studies into a reliable list of appropriate GFs/cells/biomaterials combinations required to generate a well-structured and functional engineered tissue like bone.