Summary: Human BK polyomavirus (BKV) nephropathy (BKN) remains one of the most common causes of renal allograft failure. The prevalence of BKN varies from 1% to 10% and graft loss following onset of BKN ranges from 18% to 80%. Even though BKV was isolated in 1971, the first nephropathy caused by it was diagnosed more than 20 years later. It was associated with the introduction of more potent immunosuppressive drugs, including tacrolimus and MMF. To date, there is no effective therapy against BKV, the crucial approach is to prevent BKN in viruric or viremic patients. Viruria and viremia precede the development of BKN. Routine screening for BKV DNA by PCR in urine or blood with subsequent immunosuppression reduction during the first 2 years post transplant is recommended. Persistent high viremia is associated with the greatest risk of BKN, but low viral load seems not to affect long-term outcomes. The gold standard for BKN diagnosis remains renal biopsy with SV40 staining. There is no established consensus on the treatment of BKN. Reduction in immunosuppression is crucial for clearance of the virus. Discontinuation of antiproliferative drugs, CNI dose reduction by 25–50% are the most common approaches. The potential of mTOR inhibitors to inhibit BKV replication and preserve protective immunity has been reported. The polyoma virus activates the protein Akt/mTOR pathway to trigger its replication and mTORi may inhibit this pathway. Data from clinical trials with everolimus shows a lower rate of BKV in patients receiving mTOR inhibitors when compared with patients on CNI or MMF. Conversion to mTORi is an attractive alternative to CNI reduction and de novo mTORi introduction in high-risk patients is also suggested. Reduction of immunosuppression is a risk factor for acute and especially chronic rejection. Renal function monitoring at 1–2 week intervals and DSA screening are recommended to provide a balance between the risk of BKN and rejection risk. Meta-analysis of 40 studies did not show any graft survival benefit with the addition of cidofovir or leflunomid. Effective inhibition of BK replication by fluoroquinolones was recently reported. Re-transplantation after allograft loss due to BKN is not a contraindication in the case of negative BK viremia. Transplant nephrectomy is not necessary. Further research on screening, immune monitoring, treatment strategies of BKV is required.