Hematopoietic cell transplant (HCT) activity is increasing worldwide due to safer techniques, widening indications, and more availability of donors. New HCT centers have recently been established in many developing countries including Asian and African countries. Due to limited resources, logistic, political, and social issues in developing countries, the treatment of orphan diseases like graft-versus-host disease (GVHD) can be challenging. We intended to delineate the current issues that institutions and clinicians face in managing GVHD. We conducted a comprehensive systematic electronic review of peer-reviewed published articles on GVHD management in developing countries. We used PubMed, Cochrane, and Embase databases as our primary source of data. Studies that were included described the treatments for both acute and chronic GVHD. Consensus on the use of high-dose methyl-prednisone and prednisolone as the initial therapy was widely accepted and used in practice. Socio-economic factors were found to be the major factor involved in GVHD management in lower income patients. Delayed diagnosis and treatment, lack of availability of healthcare professionals, lack of knowledge among cancer patients, and poverty are major concerns in the developing world. For optimal management, HCT programs should develop systems in place for long-term follow-up of HCT survivors and have a low threshold to initiate treatments for GVHD early. Awareness and health policy programs must be initiated at the grass-root level for long-term management of these survivors in developing countries.