Transplantation of solid organs has been successful in large part due to the development of immunosuppressive regimens that have controlled the recipient's immune system from rejecting the allograft. By suppressing recipient T lymphocytes with cyclosporin or tacrolimus or reversing rejection with antilymphocyte agents such as ATGAM or OKT3, rejection has become a rare cause of allograft loss. (Jain et al., 2000) The ‘‘trade off’’ for this non-specific immunosuppression is the increased risk of the patient contracting opportunistic infections (i. e. viral, fungal and protozoal organisms) and increased risk of malignancies. (Fung et al., 2001) In 1968, lymphoid tumors were first described in transplant patients with a subgroup of these termed ‘‘pseudolymphomas’’ in recognition of their ability to undergo regression after reduction of immunosuppression. (Starzl et al., 1984) ‘‘post-transplant lymphoproliferative disease’’ (PTLD) is now a well recognized complication of solid organ transplantation and therapeutic immunosuppression. As a result, PTLD is a major concern in the post transplant period and also a very complex disease, that encompasses a spectrum of lymphoproliferative disorders that can rise from either cells of B, T or natural killers cell origin. We will focus on the B cell type lymphoproliferative disorders in this chapter. This type is by far the most common and is usually associated with Epstein-Barr virus (EBV) infection. By definition, PTLD is a heterogeneous lymphoproliferation, ranging from benign B cell hyperplasia to aggressive B cell lymphoma, that arise in the setting of bone marrow or solid organ transplantation.