Myelodysplastic syndromes are a collection of clonal hematopoietic disorders with a wide range of clinical manifestations and eventual outcomes. Accurate prediction of a patient's prognosis is useful to define the risk posed by the disease and which treatment options are most appropriate. Several models have been created to help predict the prognosis for patients with myelodysplastic syndromes. The International Prognostic Scoring System (IPSS) has been the standard tool used to risk stratify MDS patients since its publication in 1997. Other models have since been created to improve upon the IPSS, including the recent Revised International Prognostic Scoring System. Most models include the presence or severity of peripheral blood cytopenias, the proportion of bone marrow blasts, and specific karyotype abnormalities. Other factors including age, performance status, co-morbidities, transfusion dependence, and molecular biomarkers can further refine the prediction of prognosis in some models. Novel, disease specific biomarkers with prognostic value in myelodysplastic syndromes including cell surface markers, gene expression profiles, and high resolution copy number analyses have been proposed but not yet adopted clinically. Somatic abnormalities in recurrently mutated genes are the most informative prognostic biomarkers not currently considered by clinical risk models. Mutations in specific genes have independent prognostic significance and, unlike cytogenetic abnormalities, are present in the majority of myelodysplastic syndrome cases. However, mutational information can be complex and there are challenges to its clinical implementation. Despite these limitations, DNA sequencing can refine the prediction of prognosis for myelodysplastic syndrome patients and has become increasingly available in the clinic where it will help improve the care of patients with myelodysplastic syndromes.