In the last decade the incidence of BK virus infection has increased in renal transplant recipients and become an important factor negatively influencing graft outcome. BK virus infection cannot be attributed to a single immunosuppressive agent or regimen. The risk of BKV infection is related to the overall load of immunosuppression, which is determined not only by immunosuppressive drugs but also by the humoral and cellular immunity of the recipient. Reduction in immunosuppression at this time appears to be the best available approach to the treatment of established BKVN. Assays are lacking that are able to measure the degree of immunosuppression in a given patient at a given time after transplantation. The balance between a sufficient yet nontoxic immunosuppressive regimen remains a major problem in preventing complications such as BK virus nephropathy. This article will focus on the influence of immunosuppressive medication on the development of BKVN. The role of other aspects such as viral virulence, humoral and cellular immunity or renal specificity will be shortly discussed.