Viral nephropathies, particularly those caused by polyomaviruses of the BK-virus strain are serious complications following renal transplantation. To date, there is no firmly established treatment and between 30-65% of patients with this diagnosis are reported to lose their graft within one year of diagnosis. A number of antiviral agents have been tried to help to reduce BK viral replication. However, no antiviral drug with proven efficacy against the BK virus has been licensed yet. Though cidofovir and leflunamide can be used together with a reduction in immunosuppression, the clinical effectiveness of these treatment strategies is quite questionable. Here we present two patients with polyoma virus infection. Both of them have received renal transplantation from cadaveric donors. Although their graft function was well immediately after the transplantation, their serum creatinine level found to be increased during the 3rd months of follow-up. Renal biopsy and serologic studies revealed findings consistent with polyoma virus infection. Immunosuppressive treatment was reduced in both patients and they were treated with cidofovir, leflunamide and cyprofloksasin. However, patient’s renal functions did not respond to any treatment strategies and they both have lost their graft during follow-up. After more than a decade, BK virus nephropathy remains a significant post transplant challenge. However, still there is a lack of adequate randomized controlled studies and no consensus view regarding appropriate antiviral therapy. Both cidofovir and leflunamide seem to have no effect on the prognosis of the BK nephropathy in our cases. Thus, there is an urgent need to randomized and controlled studies with a higher number of patients.