The myelodysplastic syndromes (MDS) are a collection of clonal myeloid neoplasms characterized by bone marrow failure and cytopenias. Patients classified with higher-risk disease include those with intermediate-2 or high-risk disease as classified by the International Prognostic Scoring System (IPSS). These patients represent 29% of the MDS population and were originally reported to have a median survival without therapy of only 0.4 for high-risk patients and 1.1 years for intermediate-2 risk patients. The most significant treatment goals in these patients involve prolonging the time to acute myeloid leukemia progression and extending overall survival. Quality of life, symptom control, and transfusion independence are also important. The National Comprehensive Cancer Network guidelines divide treatment options for this population into high- and low-intensity therapies. High-intensity therapies include cytarabine-based remission induction chemotherapy and hematopoietic stem cell transplantation. Transplantation is the only treatment option with the ability to cure; however, many MDS patients may not qualify due to age or comorbidities. Low-intensity therapies include the DNA methyltransferase inhibitors azacitidine and decitabine. Recently, azacitidine demonstrated the ability to extend survival by as much as 74% despite a modest complete response rate. This review examines the classification and diagnosis of higher-risk MDS patients, the management goals for these patients, clinical experience involved with treatments, guidelines, and recommendations for therapeutic options.