Periprosthetic joint infection (PJI) is a potential complication in any prosthetic joint, even in the absence of known risk factors. However, effective minimization of the risk for PJI requires elimination of known factors that increase the opportunity for exposure of the joint to pathogens or limit the body's ability to eliminate intra-articular pathogens. Known risk factors for PJI can be categorized into patient-related, surgery-related, inpatient postoperative, and long-term factors. While overlap of factors can occur between these groups, it is important to appreciate that the presence of these risks at any point increases the opportunity for the development of PJI. This chapter discusses the mechanism and impact of the factors that compose these groups.