One of the best examples of the bench-to-bedside paradigm in recent years could be the myelodysplastic syndromes (MDS). New insight into the pathophysiology of this heterogeneous group of diseases has led to relevant clinical changes. We have now the World Health Organization classification of MDS, the International Prognostic Score System to evaluate risk according to some clinical and laboratory parameters, and the approval by most of the regulatory agencies around the world of 5-azacitidine, decitabine and lenalidomide to treat MDS patients. In the last decade a robust body of evidence supports the importance of angiogenesis and angiogenesis related molecules as having a key role in the pathophysiology of hematologic malignancies including of MDS. A group of researchers around the globe is testing drugs with angiogenesis-regulatory characteristics with some success. Experience from those trials has shown angiogenesis in MDS as a dynamic process, a "moving target". Lenalidomide hit one and, although experience is being gained the complete answer is not there yet. Combinations of drugs with different mechanisms of actions are options that need to be tested. Herein we present some of the accumulated experience with these novel antiangiogenic-drugs.