In the past, the diagnosis and treatment of periprosthetic joint infection (PJI) in joint arthroplasty has often been frustrating for orthopaedic surgeons. The application of 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 this biofilm mode of microbial infection can help to explain the phenomenon of culture-negative infection as well as 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 PJI. This is a review of the current preclinical knowledge of biofilm in relation to PJI with an overview of current practices applied in the diagnosis, treatment, and prevention of biofilm formation in this setting.