Interferon‐α and cytotoxic chemotherapy may be effective treatment modalities for the post‐transplant lymphoproliferative disorder. Interferon‐α may result in a complete response in up to 40% of patients, while chemotherapy may be effective in 75% of those failing local surgical excision, a reduction in immunosuppression, and an antiviral agent. Interferon may be used early after diagnosis in patients with relatively slowly growing tumors. Chemotherapy should be selected for patients with bulky, rapidly growing malignancies. The toxicity of chemotherapy may be minimized by discontinuing maintenance immunosuppression during chemotherapy, administering GCSF, and providing antimicrobial prophylaxis. Rejection is minimized by the reintroduction of maintenance immunosuppression when the patient is no longer neutropenic.