Allogeneic hematopoietic stem cell transplantation (HCT) is still the only treatment modality with curative potential for patients with myelodysplastic syndromes. While early transplant-related mortality has improved during the last years, relapse risk following HCT still remains high, especially in older patients undergoing reduced-intensity conditioning. Therefore, when considering allogeneic HCT, in the absence of randomized data, emphasis should be put on patient selection and optimization of the pre-transplant and post-transplant period. In addition to a thorough comorbidity evaluation, risk stratification considering age, cytogenetics, grade of cytopenia, disease-related quality of life, as well as discussion of available treatment alternatives, are mandatory to decide when and how to perform allogeneic HCT. Since therapeutic options are often limited in patients relapsing after HCT, preventing relapse through maintenance strategies or minimal residual disease-directed therapy remains a central goal of current clinical research.