The article discusses graft-versus-host disease (GVHD), a major complication of allogeneic hematopoietic cell transplantation (HCT). GVHD occurs when donor T cells attack the recipient's tissues, primarily due to mismatched human leukocyte antigens (HLA). The development of GVHD is influenced by both HLA and non-HLA genetic factors, including minor histocompatibility antigens. The incidence of GVHD is directly related to the degree of HLA mismatch, with higher mismatch leading to increased risk. Non-HLA genetic differences can also contribute to GVHD, especially in HLA-identical grafts. Acute GVHD typically affects the skin, gastrointestinal tract, and liver, with clinical features including rash, diarrhea, and liver dysfunction. Chronic GVHD, which can develop months to years after HCT, is more complex and often autoimmune in nature, affecting multiple organs. The pathophysiology of GVHD involves the activation of antigen-presenting cells (APCs), donor T cell activation, and subsequent tissue damage. Key factors include the role of cytokines like TNF-α, IL-10, and IFN-γ, as well as the involvement of regulatory T cells and natural killer T cells. Prevention strategies for GVHD include T cell depletion, calcineurin inhibitors like cyclosporine and tacrolimus, and other immunosuppressive agents. Treatment of acute GVHD primarily involves corticosteroids, with additional therapies such as extracorporeal photopheresis and TNF-α inhibitors showing promise. Chronic GVHD is managed with a variety of immunosuppressive agents, though responses can be unpredictable. Supportive care is crucial for GVHD patients, involving infection prophylaxis, management of toxicities from immunosuppressive drugs, and monitoring for complications. Future directions include the use of regulatory T cells and improved biomarkers for early detection and treatment. As the number of unrelated donor transplants increases, the need for effective GVHD management strategies becomes more urgent.The article discusses graft-versus-host disease (GVHD), a major complication of allogeneic hematopoietic cell transplantation (HCT). GVHD occurs when donor T cells attack the recipient's tissues, primarily due to mismatched human leukocyte antigens (HLA). The development of GVHD is influenced by both HLA and non-HLA genetic factors, including minor histocompatibility antigens. The incidence of GVHD is directly related to the degree of HLA mismatch, with higher mismatch leading to increased risk. Non-HLA genetic differences can also contribute to GVHD, especially in HLA-identical grafts. Acute GVHD typically affects the skin, gastrointestinal tract, and liver, with clinical features including rash, diarrhea, and liver dysfunction. Chronic GVHD, which can develop months to years after HCT, is more complex and often autoimmune in nature, affecting multiple organs. The pathophysiology of GVHD involves the activation of antigen-presenting cells (APCs), donor T cell activation, and subsequent tissue damage. Key factors include the role of cytokines like TNF-α, IL-10, and IFN-γ, as well as the involvement of regulatory T cells and natural killer T cells. Prevention strategies for GVHD include T cell depletion, calcineurin inhibitors like cyclosporine and tacrolimus, and other immunosuppressive agents. Treatment of acute GVHD primarily involves corticosteroids, with additional therapies such as extracorporeal photopheresis and TNF-α inhibitors showing promise. Chronic GVHD is managed with a variety of immunosuppressive agents, though responses can be unpredictable. Supportive care is crucial for GVHD patients, involving infection prophylaxis, management of toxicities from immunosuppressive drugs, and monitoring for complications. Future directions include the use of regulatory T cells and improved biomarkers for early detection and treatment. As the number of unrelated donor transplants increases, the need for effective GVHD management strategies becomes more urgent.