Bone tissue engineering (BTE) represents a multidisciplinary research field involving many aspects of biology, engineering, material science, clinical medicine and genetics to create biological substitutes to promote bone regeneration. The definition of the most appropriate biomaterials and structures for BTE is still a challenge for researchers, aiming at simultaneously combining different features such as tissue generation properties, biocompatibility, porosity and mechanical strength. In this scenario, among the biomaterials for BTE, silk fibroin represents a valuable option for the development of functional devices because of its unique biological properties and the multiple chances of processing. This review article aims at providing the reader with a general overview of the most recent progresses in bone tissue engineering in terms of approaches and materials with a special focus on silk fibroin and the related mechanisms involved in bone regeneration, and presenting interesting results obtained by different research groups, which assessed the great potential of this protein for bone tissue engineering.