Malacoplakia is a rare inflammatory disorder seen most often in the urinary tract, where it is highly associated with coliform infection. Although first recognized by pathologists in 1902, it has received little attention from the infectious disease community. While there remains much uncertainty regarding the specific cause of malacoplakia, it appears to be associated with a defect in intracellular killing of ingested microorganisms by macrophages. We report a case of bilateral renal parenchymal malacoplakia that presented as fever of unknown origin, and we review 33 previously identified cases. Renal malacoplakia has traditionally been associated with high morbidity and mortality. More recently, treatment with antimicrobial agents such as trimethoprim or ciprofloxacin has yielded a better outcome than had been documented with other therapy. Malacoplakia should be considered in the evaluation of fever of unknown origin or of relapsing or refractory urinary tract infection. Therapy with antimicrobial agents capable of intracellular penetration is recommended.