Graft-versus-host disease (GVHD) after allogeneic stem-cell transplantation causes significant morbidity and mortality. An important site of GVHD is the gastrointestinal (GI) tract because development of acute GI GVHD is prognostic of overall survival. The standard of care to treat acute GI GVHD is systemic corticosteroids and immunosuppressants; however, the use of these therapies can cause life-threatening opportunistic infections. To limit the adverse effects of systemic immunosuppression, the topically active corticosteroid beclometasone dipropionate has been investigated in case studies and in randomized placebo-controlled trials for the treatment of acute GI GVHD. In this review, we appraise these studies with beclometasone dipropionate, and discuss future randomized studies to clarify the role of beclometasone dipropionate for the treatment and prevention of acute GVHD. At present, more data are required before the addition of beclometasone dipropionate to systemic corticosteroids for the treatment of acute GVHD can be considered the standard of care.