For heterogeneous myelodysplastic syndromes (MDS), patient management is still a challenge. Despite the progress achieved in recent years, there is need for improvement at least for specific situations such as failure of hypomethylating agents or in patients with thrombocytopenia or with anemia failing erythropoiesis stimulating agents. This review covers studies for MDS presented at the American Society of Hematology (ASH) 2016 annual meeting. New treatment approaches, for which results from phase 1/2 studies were reported, will now move into phase 3 and hopefully into clinical practice in the future. Choosing the right agent and individualizing treatment will be the next challenges.