Post transplant lymphoproliferative disorder is the second most frequent malignancy following solid organ transplantation with an incidence of about 0.5 to 20% in the transplant population. The incidence of PTLD is greatly dependent on the type of transplant and the intensity of immunosuppression in induction and maintenance. With recent improvements in the management of immunologic and infectious complications in solid organ transplantation, PTLD is becoming a major challenge and represents a serious and often devastating complication after SOT. This is an analysis of different therapeutic options in PTLD with a strong focus on chemotherapy. Our studies using sequential treatment with rituximab and CHOP chemotherapy after patients failed to respond significantely to an upfront reduction of immunosuppression clearly demonstrate that sequential treatment is feasible in adult solid organ transplant recipients, and shows a superior efficacy rate and safety profile compared with historic data in the treatment of PTLD. Further studies have improved therapeutic options for patients with relapsed PTLD. Sequential therapy with CHOP after 4 courses rituximab therapy achieved a CR rate of 65% and an overall response rate of 90%, with a much lower toxicity than usually reported for CHOP in the literature. While there was no severe rituximab related toxicity, CHOP associated severe neutropenia occured in 38% of chemotherapy cycles and severe infections were observed in 16% of patients. However, the treatment related mortality was below 10%. Disease free survival after 1 and after 2 years is 81% in this study at the moment. Notably, of the patients that were treated according to protocol, 64% are progression-free at 2 years. The purpose of the following studies was to analyze the efficiency and safety of chemotherapy salvage therapies in adult recipients of solid organ transplant with a second progression of PTLD after 1st-line therapy. After 1st-line rituximab CHOP salvage therapy achieves a favorable overall response rate of 70% in this setting, indicating that PTLD generally remains chemotherapy-sensitive after progression following first-line rituximab. Although the treatment associated toxicity for CHOP was significant, lethal infectious toxicity was not observed in this study. However, some patients had to be switched to less toxic monotherapies because CHOP was not tolerated and both patients subsequently experienced disease progression. After 1st-line CHOP-based chemotherapy protocols the effect of salvage therapy is greatly dependet on upfront treatment and comorbidity. There is a higher treatment associated toxicity even for less toxic regimens like carboplatin/etoposide or single agent bendamustin for patients with an ECOG greater than 2 or with an impaired renal function. However, both regimens do achieve an overall survival of about 50% after 1 year and 17% after 5 years without high dose therapy and autologous stem cell transplantation. Classical salvage therapy using DHAP, DexaBEAM and ICE (+/- high dose therapy and ASCT) are not suitiable for the majority of patients with PTLD.