Musculoskeletal infection is a clinical problem with significant direct healthcare costs. The prevalence of infection after closed, elective surgery is frequently estimated to be less than 2%, but in severe injuries, posttraumatic infection rates have been reported as 10% or greater. Although clinical infections are found outside the realm of medical devices, it is clear that the enormous increase of infections associated with the use of implants presents a major challenge worldwide. This review summarizes recent advances in the understanding, diagnosis, and treatment of musculoskeletal infections.