Polyomavirus BK (BKV) is ubiquitously present amongst the general population establishing a latent, seemingly asymptomatic infection in immunocompetent individuals. In transplant recipients, however, BKV reactivation is common and can lead to distinctive pathological entities in different patient groups: in renal transplant (RT) recipients, it is associated with nephropathy (BKVN) and ureteral stenosis, and in haematopoietic stem cell transplant (HSCT) recipients with haemorrhagic cystitis (HC). Furthermore, BKV employs several potentially oncogenic mechanisms to promote its replication in cells and has been inconsistently linked to the development of malignancies. BKVN is currently a major cause of allograft failure in RT recipients. HC causes prolonged hospital stay and increased mortality in HSCT recipients. Despite its discovery more than 40 years ago, few advances have been made with regard to therapeutic strategies. Current therapies aim to restore the impaired immune response, e.g. by lowering immunosuppressive agents in RT recipients. However, this is a double-edged sword since it also increases the chance of rejection. Therefore, more specific and effective treatment strategies are urgently needed. Here, we will review the current knowledge on the structure and lifecycle of BKV, characteristics of the BKV-specific immune response, its clinical manifestations and the strengths and limitations of available treatments Polyomavirus BK (BKV) is ubiquitously present amongst the general population establishing a latent, seemingly asymptomatic infection in immunocompetent individuals. In transplant recipients, however, BKV reactivation is common and can lead to distinctive pathological entities in different patient groups: in renal transplant (RT) recipients, it is associated with nephropathy (BKVN) and ureteral stenosis, and in haematopoietic stem cell transplant (HSCT) recipients with haemorrhagic cystitis (HC). Furthermore, BKV employs several potentially oncogenic mechanisms to promote its replication in cells and has been inconsistently linked to the development of malignancies. BKVN is currently a major cause of allograft failure in RT recipients. HC causes prolonged hospital stay and increased mortality in HSCT recipients. Despite its discovery more than 40 years ago, few advances have been made with regard to therapeutic strategies. Current therapies aim to restore the impaired immune response, e.g. by lowering immunosuppressive agents in RT recipients. However, this is a double-edged sword since it also increases the chance of rejection. Therefore, more specific and effective treatment strategies are urgently needed. Here, we will review the current knowledge on the structure and lifecycle of BKV, characteristics of the BKV-specific immune response, its clinical manifestations and the strengths and limitations of available treatments methods.