Myelodysplastic syndromes are clonal myeloid neoplasms that primarily present in older adults. Although leukemia develops in approximately 25% to 30% of individuals, the significantly shortened survival in this population is attributed more commonly to nonleukemic causes. The current prognostic scoring systems for leukemia and overall survival based on disease characteristics are becoming increasingly sophisticated and accurate with the incorporation of molecular data. The addition of patient-related factors such as comorbidity, disability, frailty, and fatigue to these new models may improve their predictive power for overall survival, treatment toxicity, and health care costs. To improve the generalizability of clinical trial results to the real world, geriatric assessment testing should become a standard of care in MDS clinical trials.