Implant-associated infections are caused by microorganisms growing in biofilms, rendering these infections difficult to diagnose and to eradicate. Delayed-onset low-grade infection is difficult to distinguish from aseptic failure, often presenting without signs of infection, but only with early loosening and persisting pain. A combination of criteria is needed for an accurate diagnosis: clinical signs and symptoms, laboratory signs of infection, microbiology, histology, and imaging. The treatment goals in prosthetic joint-associated infection are eradication of infection and an optimal functional result. The goal in internal fixation device-associated infection is consolidation of the fracture and avoidance of chronic osteomyelitis. Successful treatment requires an adequate surgical procedure combined with long-term antimicrobial therapy, ideally with an agent acting on adhering biofilm microorganisms. This article reviews the epidemiology, pathogenesis, diagnosis, and management of implant-associated infections, and presents pathogenesis and risk of hematogenous infection.