Abstract Nanotechnology has the potential to provide a plethora of novel tools for application in translational orthopedic research and revolutionize the biomedical fields. The demerits of the clinically available orthopedic implants include poor osseointegration at the tissue-implant interface, which subsequently results in loosening due to low mechanical fixation, immunological rejection, production of wear debris, and implant-related infections. Nanomaterials are promising for orthopedic applications because of their excellent tribological properties, wear and tear resistance, sustained drug delivery, osseointegration, and tissue regeneration capabilities. Nanostructured materials play a pivotal role in orthopedic research owing to their size range and the ability to mimic the features and hierarchical structure of native bones. They offer diverse functions like better bone fracture repair, promote cell growth, reduce infection rates and biofilm formation. New-generation nanostructured ceramics, polymers, metals, and carbon materials have opened new avenues in orthopedic research. This chapter highlights the application of the nanomaterials in the domain of bone tissue engineering, diagnosis, implant-related infections, bone tumor, and bone healing. Different nanomaterials and several fabrication techniques are being envisaged comprehensively for both laboratory and industry scale. The chapter also briefly acknowledges current reports of safety of nanomaterials in different cell lines along with regulatory requirements for orthopedic devices in regulated and semiregulated markets. Newly emerging smart nanomaterials and 3D printing technology for fabrication of patient-tailored orthopedic implants are also mentioned in brief.