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The association of certain microorganisms, such as Staphylococcus epidermidis, Staphylococcus aureus, and β-hemolytic streptococci, with prosthetic joint infection (PJI) has been recognized for many years. To our knowledge, a systematic review of the presentation and management of less commonly encountered species of coagulase-negative staphylococci, nutritional-variant streptococci, aerobic non-spore and spore forming Gram-positive or anaerobic bacteria is not available. We therefore sought to provide a comprehensive literature review of PJI due to these microorganisms that will provide a valuable and quick reference for clinicians caring for these patients. We conducted a Medline search of all case reports and case series of PJI due to unusual aerobic and anaerobic bacteria. The presentation, surgical, and medical management strategies were reviewed. Appropriate medical and surgical management of such infections is complex and evolving as newer diagnostic tests, surgical techniques and antimicrobials become available. Management of patients with these infections requires close collaboration between the orthopaedic surgeon, infectious disease specialist and microbiology laboratory.Level of Evidence: Level V, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.