Acute graft-versus-host disease remains a devastating complication following hematopoietic cell transplantation, resulting in increased morbidity and mortality. Vast research efforts continue to refine or develop new means of prediction, assessment, prevention, and treatment of this syndrome. Recent updates in acute graft-versus-host disease include more definitive guidance and definitions for its grading and diagnosis. Biomarker use is being incorporated into early stages following hematopoietic cell transplantation to aid in the detection and prediction of long-term outcomes. New preventive strategies under investigation include the use of vedolizumab or tocilizumab as upfront prophylaxis. Finally, although steroids remain the backbone of therapy once treatment is warranted, the efficacy of several agents including vedolizumab, tocilizumab, ruxolitinib, and α1 antitrypsin are being evaluated as potential therapeutic options. © 2020 Pharmacotherapy Publications, Inc.