Myelodysplastic syndromes (MDS) comprise a heterogeneous group of clonal hematologic malignancies characterized by a hypercellular bone marrow and morphologic dysplasia in one or more lineage (i.e., myeloid, erythroid, or megakaryocytic), presenting clinically with leukopenia, anemia, and/or thrombocytopenia and with a propensity to transform to acute myelogenous leukemia. Newer technologies such as next-generation sequencing have allowed better understanding of the genetic landscape in MDS. Nearly 80 % of MDS patients have at least one mutation, and approximately 40 recurrent somatic mutations have been identified to occur in >1 % of cases. Many of these mutations are relevant for prognosis, help with selection of therapy, and/or have specific targeted treatment options. In this article, we will explore the impact of molecular testing on diagnosis, prognosis, and treatment decisions in patients with suspected MDS.