Polyomavirus infection in immunosuppressed transplant patients is in most cases an asymptomatic reactivation of a latent infection that can, however, progress to manifest disease. JC virus causes progressive multifocal leukoencephalopathy, a rare complication with poor outcome. BK virus infection has been associated with hemorrhagic cystitis of late onset in bone marrow recipients and with ureteral stenosis in renal allograft recipients. More recently, BK virus has been identified in renal transplant recipients as the cause of progressive graft dysfunction and loss. The diagnosis of BK virus nephropathy requires allograft biopsy, revealing typical viral intranuclear inclusion bodies, and, in typical cases, damage of tubules. Urine cytology and the detection of BK virus DNA in plasma helps to identify and manage patients with BK virus nephropathy. Because of the lack of effective antiviral therapy, current treatment attempts aim at lowering the degree of immunosuppression in order to regain control over polyomavirus replication.