The development in the therapeutic landscape of myelodysplastic syndromes (MDS) has substantially lagged behind other hematologic malignancies with no new drug approvals for MDS for 13 years since the approval of decitabine in the United States in 2006. While therapeutic concepts for MDS patients continue to be primarily defined by clinical-pathologic risk stratification tools such as the International Prognostic Scoring System (IPSS) and its revised version IPSS-R, our understanding of the genetic landscape and the molecular pathogenesis of MDS has greatly evolved over the last decade. It is expected that the therapeutic approach to MDS patients will become increasingly individualized based on prognostic and predictive genetic features and other biomarkers. Herein, we review the current treatment of lower-risk MDS patients and discuss promising agents in advanced clinical testing for the treatment of symptomatic anemia in lower-risk MDS patients such as luspatercept and imetelstat. Lastly, we review the clinical development of new agents and the implications of the wider availability of mutational analysis for the management of individual MDS patients.