Despite new developments in innovative and potentially targeted drugs like hypomethylating agents (HMA), allogeneic hematopoietic stem cell transplantation (HCT) is still the only potentially curative treatment option for patients with myelodysplastic syndromes (MDS). Improvements in donor selection and supportive care, as well as the introduction of reduced-intensity conditioning, have improved the feasibility of this approach by reducing early mortality. As a result, the number of allogeneic HCTs performed in MDS patients mainly above the age of 60 years has significantly increased over the last decade. However, the main drawbacks of this procedure, including graft-versus-host disease (GVHD) and hematologic relapse, remain a challenge in daily patient care. Thus, optimization of the pretransplant remission status and post-transplant outcome, eg, by new GVHD prophylaxis regimens or pharmacological maintenance or pre-emptive therapy of minimal residual disease to prevent relapse, is an important goal of current clinical research. There is an urgent need for prospective randomized trials to identify the subgroup of MDS patients who could achieve a better long-term disease control by allogeneic HCT compared to treatment with current standards of care, including HMA.