Chronic graft-versus-host disease (cGVHD) represents a common long-term complication after allogeneic hematopoietic stem cell transplantation (HSCT). It imposes a significant morbidity burden and is the leading cause of non-relapse mortality among long-term HSCT survivors. cGVHD can manifest in nearly any organ, severely affecting the quality of life of a transplant survivor. While the mainstay of treatment has remained systemic immunosuppression with glucocorticoids, progress has been made within the last few years with approvals of three oral agents to treat steroid-refractory cGVHD: ibrutinib, ruxolitinib, and belumosudil. Iatrogenesis contributes a significant portion of the morbidity experienced by patients with cGVHD, primarily from glucocorticoids. This review highlights the myriad impacts of cGVHD, including and beyond the traditional organ systems captured by the National Institutes of Health Consensus Criteria, including iatrogenic complications of long-term immunosuppression. It presents the implications of cGVHD and its treatment on cardiovascular and metabolic health, bone density, endocrine function, sexual health, and ocular and pulmonary disease and outlines a framework around the comprehensive multidisciplinary approach for its evaluation and management.