A systematic review of the presentation and management of prosthetic joint infection (PJI) due to zoonotic microorganisms, fungi, mycobacteria and other unusual microorganisms is not available. We therefore sought to provide a resource for the practicing orthopaedic surgeon which will serve as a guide for making appropriate decisions in managing such rare, but potentially problematic conditions. We conducted a Medline search of all case reports of PJI due to these unusual microorganisms. Our review of the current literature showed the diagnosis of PJI due to zoonotic microorganisms, fungi, mycobacteria and other unusual microorganisms typically necessitates specialized diagnostic tests. Maintaining a high index of suspicion in diagnosis of such unusual microorganisms and requesting the appropriate laboratory tests at the time of surgical débridement is crucial for determining the microbiologic etiology of these infections. The appropriate medical and surgical management of such infections is complex and often requires the use of special antimicrobials with which the orthopaedist may not be familiar. Collaboration with an infectious disease specialist is advisable when treating these infections.