The management of the myelodysplastic syndromes (MDS) requires insight into the complex biology of the disease. Despite this challenge, two recent developments have contributed significantly to advancements in the treatment of MDS: (i) improvements in classification systems and prognostic models; and (ii) the emergence of US FDA-approved agents such as lenalidomide, azacitidine and decitabine. Prior to these developments, supportive care measures consisting of blood and platelet transfusions, haematopoietic growth factors and antimicrobials remained standard of care for the treatment of MDS. As a result of these developments, clinicians are able to provide patient-tailored therapy for specific MDS subgroups. Clinical trials addressing combination therapies with multiple investigational agents as well as novel combination regimens are ongoing. This review focuses on supportive care modalities, the approved agents indicated for the treatment of MDS and future directions for the treatment of MDS, including agents under clinical investigation.