Post-transplant lymphoproliferative disorder (PTLD) is an increasingly recognized complication of solid organ and hematopoietic stem cell transplantation. PTLD represents a spectrum of polyclonal and monoclonal lymphoproliferation, generally of B cells. Prompt diagnosis is key and requires a high index of suspicion. An increasing variety of highly effective therapies, including immune modulation via reduction in immunosuppression, monoclonal antibodies, and cellular therapy, have dramatically improved the cure rates of this once devastating disease.