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Advances in immunosuppression have lowered the acute rejection rates in kidney transplant recipients but have impacted negatively on the viral infection rates. Polyomavirus-associated interstitial nephropathy (PyVA N) affects up to 10% of kidney transplant recipients and can progress to irreversible allograft failure in up to 45% of affected cases. Nowadays, thanks to increased awareness of PyVA N and improved diagnostic techniques, the rate of graft loss has decreased, most markedly in centers with active screening and intervention programs. The diagnosis of PyVA N is made by allograft histology. However, systematic screening by quantitative molecular-genetic techniques allows intervention in the early stages of the disease, before the occurrence of irreversible parenchymal changes. So far, the only proven measure affecting PyVA N progression and outcome is the reduction of immunosuppression. Other therapeutic approaches including cidofovir, leflunomide, fluoroquinolones and intravenous immunoglobulins have been explored, but there is no clinical evidence supporting their efficacy. It has been largely demonstrated that BKV-specific T-cell immunity plays a pivotal role in controlling viral replication and disease progression. For this reason viral-specific T-cell immunity can help in monitoring PyVA N. Protocols of adoptive T-cell transfer based on infusion of BKV-specific T cells are the object of many studies and should be considered an innovative treatment approach for PyVA N.