Acute graft-vs-host disease (GVHD) is a T cell-mediated reaction in which donor T lymphocytes attack host tissue in the setting of immunosuppression. The most common cause of acute GVHD is allogeneic stem cell transplantation, with solid-organ transplantation being a much less common cause. Early diagnosis and treatment are imperative to decrease morbidity and mortality. Dermatologists play a fundamental role in the diagnosis of this condition because skin involvement is among the earliest signs of acute GVHD. We present a case of acute GVHD following liver transplantation, focusing on diagnostic criteria and a comparison to acute GVHD following hematopoietic stem cell transplantation.