Renal transplant recipients are susceptible to infection by a wide array of pathogens. Impaired inflammatory responses due to immunosuppressive therapies suppress clinical and radiologic findings engendered by microbial invasion. As a result, patients are often minimally symptomatic and evaluation and diagnosis are delayed. Specific microbiologic diagnosis is essential both for the optimization of antimicrobial therapy and to avoid unnecessary drug toxicities. Differential diagnosis is guided by knowledge of organisms commonly involved in infection in immunocompromised hosts and understanding of the limitations of prophylactic strategies. The risk of infection in the organ transplant recipient is determined by the interaction between the individual's epidemiologic exposures and net state of immunosuppression. Epidemiology includes environmental exposures in the community and hospital, organisms derived from donor tissues and latent infections activated in the host during immune suppression. The net state of immune suppression is determined by the interaction of all factors contributing to infectious risk. Routine antimicrobial prophylaxis is aimed at common infections and unique risk factors in individual patient groups. This includes trimethoprim-sulfamethoxazole (for Pneumocystis, Toxoplasma, most Nocardia and Listeria, common urinary pathogens), perioperative (eg, anti-fungal prophylaxis for pancreas transplants), or antiviral (for herpesviruses in high risk recipients).