In the past, diagnosing and treating periprosthetic infections in joint arthroplasty have often been challenging for orthopaedic surgeons. Certain diagnostic criteria and different treatment strategies can be better directed if these infections are placed in the context of microbial biofilms. An understanding of the biofilm mode of microbial infection can help explain the phenomenon of culture-negative infection and provide an understanding of why certain treatment modalities often fail. Continued basic research into the role of biofilms in infection will likely provide improved strategies for the clinical diagnosis and treatment of periprosthetic joint infections.