INTRODUCTION: Titanium-based materials do not fulfill all of the requirements of orthopedic implants due to a mismatch in mechanical properties with bone which are prone to change during the course of bone growth. Biofunctional biomaterials are a new class of materials that show bioactivity and adaptability at any stage of bone growth. AREAS COVERED: Different biofunctional biomaterials have evolved over time that can enhance calcium phosphate (CaP) precipitation, stimulate osteogenic differentiation, and can control osteoblast gene expression. These materials include metals or metal alloys, ceramics, polymers and biocomposites. Similarly, naturally-inspired nanomaterials and nanometer surface featured modified materials can enhance bone growth if created to match bone's unique micro to nano hierarchical structure. Nanoscale manipulation of existing biomaterials can incorporate antimicrobial properties which is desirable to prevent infection and failure of orthopedic devices. EXPERT COMMENTARY: Recent research trends in biofunctional biomaterials have focused to, first, understand the bone growth mechanism and, then, mimic natural bone architecture using biomaterials. Therefore, an enhanced understanding of material properties and tissue engineering principles will lead the way forward designing biofunctional biomaterials. In the future, the role of biofunctional biomaterials and orthopedic sensors will be more pronounced in terms of musculoskeletal disease prevention, diagnosis, and treatment.