Nanotechnology applications in medicine are poised to revolutionize the prevention, diagnosis, and treatment of disease. Researchers, scientists, and physicians across various disciplines and specialties are working to develop innovative clinical tools that incorporate materials, devices, and systems engineered at the nanoscale. Surgical specialties, such as orthopedic surgery, are among those developing nanotechnology applications for clinical use. Orthopedic surgery addresses disorders of the musculoskeletal system including repair by both surgical and nonsurgical means of tendons, ligaments, muscles, bones, and nerves injured due to trauma or disease. Medical interventions targeting orthopedic conditions are becoming increasingly important given current epidemiologic trends in these conditions. The purpose of this article is to highlight current and emerging applications of nanotechnology in orthopedic surgery. Selected, clinically relevant examples are described in the categories of drugs and drug delivery, imaging, sensors, biomaterials, diagnostics, and novel therapeutics. Several promising nanomedicine applications that target orthopedic conditions are in various stages of development from basic scientific research to clinical trials to product development and commercialization. Nanotechnology applications aimed at the prevention, diagnosis, and treatment of orthopedic conditions hold great promise for improving the standard of care in orthopedic surgery in the 21st century.