This chapter presents a state of the art summary of post-transplant lymphoproliferative disorders (PTLD) to its biology, epidemiology, disease mechanisms, clinical signs, diagnosis, treatment and prognosis. PTLD represent a heterogeneous group of diseases that occur as serious complications of solid organ transplantation and hematopoietic stem cell transplantation. The incidence of PTLD in children is generally higher than that in adults as children often have negative serology and thus increased susceptibility for Epstein-barr virus (EBV) prior to transplantation. Risk factors for PTLD are EBV status at time of transplantation, EBV mismatch, type of transplanted organ, and type and duration of immunosuppressive regimens. Diagnosis of PTLD relies on observation of clinical symptoms, detection of EBV in peripheral blood, imaging evaluation of nodal and extranodal involvement, and histopathological and immunohistochemical examination of the underlying lymph node/organ. Differential diagnoses for PTLD include specific and nonspecific lymphoplasmacytic infiltrations associated with infection, graft rejection, and graft-versus-host disease.