Polyomavirus-associated nephropathy (PVAN) remains an important infectious complication after renal transplantation, affecting 1-10% of recipients and causing graft loss in approximately 50% of cases. With the lack of effective antiviral therapy, intensive monitoring for BK virus (BKV) using nucleic acid testing or urine cytology--in combination with a reduction of immunosuppressive therapy--is advocated to detect and prevent BKV reactivation and PVAN, respectively. In this Review, new insights into BKV biology and the development of PVAN are discussed. Clinical diagnostic approaches for the detection, surveillance and therapeutic monitoring of BKV are described. In addition, various strategies for reduction of immunosuppressive therapy are reviewed and an evaluation provided of the mechanisms of action and clinical effects of currently used adjuvant medication such as cidofovir, leflunomide, intravenous immunoglobulins and fluoroquinolone antibiotics. Finally, novel compounds and their in vitro actions against BKV are discussed together with future prospects for specific antiviral drug development.