Post-transplant lymphoproliferative disorder (PTLD) is a recognized severe complication arising in allograft recipients treated with immunosuppressive drugs. Although not common, PTLD is one of the most frequent tumours among graft recipients, comprising 15-25% of neoplasms, compared with 5% in the general population. The introduction of cyclosporin A (CyA) in the early 1980's and the very potent new immunosuppressants such as anti-CD3 monoclonal OKT3 and FK506 have been associated with a significant rise in the incidence of PTLD and with their earlier presentation. The incidence of this malignancy varies with the organ transplanted (1-2% of renal transplant recipients) and with the nature and severity of the accompanying immunosuppressive regimen. While the precise etiology of PTLD is still unclear, significant advances have been made recently in the understanding of its pathogenesis. Most PTLD tumour cells present an activated B-cell phenotype and an unrestricted pattern of latent EBV gene products. It is generally accepted that Epstein-Barr virus (EBV) infection or reactivation and intensive anti-T lymphocyte regimens play a major role in the genesis of PTLD. They include a spectrum of EBV-related disorders ranging from lymphoid hyperplasia to frank malignant non-Hodgkin's lymphoma. Although different therapeutic attempts have been proposed, optimal treatment remains elusive. The mortality rate for monoclonal lymphomas was reported to be as high as 80%. Infusion of anti-B monoclonal antibodies seems to be a promising modality. Different preventive approaches have been proposed, including EBV sero-negative donor/recipient matching and careful monitoring of EBV infection. Cautious use of anti-rejection treatment in combination with prophylactic antiviral therapy is recommended.