The last decade has witnessed the introduction of several potent immunosuppressive agents in the field of transplant medicine. Contemporaneously, infection with BK virus (BKV) has emerged as an important complication of immunosuppression and an important cause of allograft loss after kidney transplantation. Rhandhawa et al reported the first case of BKV associated nephropathy (BKVN) in the modern era of transplantation, in 1995. Since then there has been a resurgence of interest in the epidemiology, biology and pathogenic associations of BKV especially in transplant medicine. Up to 90% of adults have serologic evidence of exposure to BKV. However, only 1-5% of normal healthy adults excrete the virus in the urine (asymptomatic viruria). Thus, for a vast majority of the population, the virus remains perfectly latent and this state of latency is of no obvious consequence. Almost all instances of disease by the BKV have been seen in immunocompromised patients. In recent years, BKV has been associated with nephropathy (BKVN) in about 5% of renal transplant patients. Once established, the disease may result in allograft loss in 45-70% of patients. Although not proven by any prospective study, BKVN causing allograft failure has been linked to immunosuppressive regimens containing tacrolimus or mycophenolate mofetil. This is noteworthy, as both these agents have been used increasingly as the primary maintenance immunotherapy in solid organ transplantation since their introduction around 1990. In addition to the immunosuppressed state, other factors like allograft injury have been thought to be involved in the pathogenesis of the disease. We believe that reactivation of the BKV from its latent state crucially depends on an immunocompromised state but more factors than one dictate precipitation of clinical end organ disease. In this Chapter, we will discuss the clinical aspects of BKV infection in the renal transplant recipient. We will focus on the role of immunosuppression as a seminal factor allowing replication of the virus. Not all patients who have replicating BKV go on to develop nephropathy: we will discuss other host factors that may constitute a' second hit' allowing replicating BKV to precipitate BKVN. Results of our recently concluded prospective study on the issue of current immunosuppressive agents in the development of BKVN will be discussed. Finally, based on our experience, we will provide some guidelines for early diagnosis and management of this disease.