From these various studies, it is apparent that the key to improving management of chronic GVHD remains elusive. Heterogeneity of patients and disease manifestations and even uncertainty in diagnosis of chronic GVHD confound all these studies. At one referral center, 15-20% of the patients referred for management of chronic GVHD were found to have no signs of the disease. Treating physicians are inconsistent in recognizing the protean manifestations of this syndrome. If patients with varying symptoms are included in heterogeneous pilot studies, interpretation of their findings may be misleading. Future studies of chronic GVHD need carefully defined eligibility, consistent therapy, and clearly defined response criteria. At present, there are two prospective randomized trials underway for treatment of chronic GVHD. One is a multicenter trial for standard-risk patients comparing prednisone and cyclosporine with or without MMF. The Children's Oncology Group is comparing the addition of hydroxychloroquine to initial therapy of chronic GVHD. The outcome from these two trials will be important in offering prospective and clear data, even if the either agent is not a big advance. An essential component of chronic GVHD medical management is ongoing supportive care over the whole length of therapy. This must include infection prophylaxis, hydration, nutrition, and careful follow-up. New strategies for abatement of chronic GVHD are essential, but more critical are new ideas to manage the immune deficiency associated with chronic GVHD, discipline in designing and executing studies, clinical caution in interpreting the outcomes, and new support systems to help patients bear the ongoing burdens accompanying this lengthy chronic illness.