In this review, we discuss current advances leading to an exciting change in implant design for orthopedic surgery. The initial biomaterial approaches in implant design are being replaced by cellular-molecular interactions and nanoscale chemistry. New designs address implant complications, particularly loosening and infection. For infection, local delivery systems are an important first step in the process. Selfprotective 'smart' devices are an example of the next generation of orthopedic implants. If proven to be effective, antibiotics or other active molecules that are tethered to the implant surface through a permanent covalent bond and tethering of antibiotics or other biofactors are likely to transform the practice of orthopedic surgery and other medical specialties. This new technology has the potential to eliminate periprosthetic infection, a major and growing problem in orthopedic practice.