Increasing attention has been recently accorded to BK and JC viruses (BKV and JCV). Both these human polyomavirus (HPV) are members of the papovavirus family which includes the simian virus SV 40. BKV and JCV infect more than 60% of the population worldwide. After primary infection, they remain harboured in the kidneys and may become reactivated in situations of immune impairment. HPV were first described in 1971. BKV was isolated in a renal transplant patient with ureteral stricture and JCV in a patient with progressive multifocal leukoencephalopathy (PML). BKV was known to be involved in post-bone marrow transplantation (BMT) hemorrhagic cystitis. In renal transplantation, BKV and JCV were initially found in the post-transplant ureteric stricture and PML. They are now recognised as a possible cause of transplant interstitial nephritis, mimicking rejection (satisfying the Banff criteria for acute rejection) or drug toxicity. In HPV nephritis there is a mixed interstitial inflammatory infiltrate with focal tubular injury; the tubular epithelium shows marked anisonucleosis, nuclear atypia and basophilic or amphophilic intranuclear inclusions. Tubulitis is frequent. DNA hybridisation or gene amplification by polymerase chain reaction usually demonstrate HPV. Although histology with viral nucleic acid detection may be helpful in differentiating viral infection and rejection, confusion between these complications may lead to either anti-rejection therapy, with the risk of over-immunosuppression, or reduction of immunosuppression, with the risk of graft loss. Confusion may also arise with inclusions of other viruses, such as cytomegalovirus, herpes virus and adenovirus. Reactivation of BKV and JCV infection was demonstrated in respectively 22.2% and 10.9% of renal transplant recipients and 55% and 6.7% of BMT patients. Unfortunately, no routine screening is available for these viruses, so this complication is probably underestimated. No specific therapy of HPV infection is currently available.