Within the MDS work-package of the European LeukemiaNet, an Expert Panel was selected according to the framework elements of the NIH Consensus Development Program. A systematic review of the literature was performed including indexed original papers, indexed reviews and educational papers, and abstracts of conference proceedings. Guidelines were developed based on a list of patient- and therapy-oriented questions, and recommendations were formulated and ranked according to the supporting level of evidence. MDS should be classified according to the 2008 WHO criteria. An accurate risk-assessment requires not only the evaluation of disease-related factors, but also of those related to extra-hematological comorbidity. The assessment of individual risk enables the identification of fit patients with a poor prognosis, who are candidates for up-front intensive treatments, primarily allogeneic stem cell transplantation. A high proportion of MDS patients are not eligible for potentially curative treatment because of advanced age and/or clinically relevant comorbidities and poor performance status. In these patients, the therapeutic intervention is aimed at preventing cytopenia-related morbidity and preserving quality of life. A number of new agents are being developed, for which the available evidence is not sufficient to recommend routine use. The inclusion of patients into prospective clinical trials is strongly recommended.