The heterogeneous nature of myelodysplastic syndromes (MDS) demands a complex and personalized variety of therapeutic approaches. Among them, allogeneic hematopoietic stem cell transplantation remains the only potentially curative option and is accessible to only a small number of fit patients. For the majority of patients with MDS, treatment strategies are nonintensive and risk-adapted (by the revised version of the International Prognostic Scoring System), ranging from iron chelation and growth factors to lenalidomide and hypomethylating agents. These approaches are noncurative and aimed instead at improving cytopenias and quality of life and delaying disease progression. These limitations underpin the need for more translational research-based clinical trials in well-defined subgroups of patients with MDS. Indeed, much progress has been made over the past decade in understanding the complex molecular mechanisms underlying MDS. Unfortunately, this has not yet translated into approval of novel treatment options. There is a particularly urgent medical need in patients failing current first-line therapies, such as with erythropoiesis-stimulating or hypomethylating agents. Nevertheless, actual developments are expected to pave the way for exciting novel therapeutic opportunities. This review provides an overview of the current therapeutic landscape in MDS focusing on recent advances in clinical and translational research.