Treatment of older adults with acute myeloid leukemia (AML) is challenging in part due to the difficulty of accurately predicting risks and benefits of available therapies. While older patients represent the majority of those with newly diagnosed disease, there remains no consensus regarding optimal therapy. Older age is associated with increased risk of treatment-related toxicity and worse survival compared to younger adults. Age-related outcome disparity in the setting of AML therapy is clearly attributed in part to differences in tumor biology conferring resistance to therapy. However, physiologic changes of aging that decrease treatment tolerance also influence outcomes and vary among patients of the same chronologic age. Measurable patient characteristics such as comorbidity and physical function can reflect the heterogeneity of physiologic aging among older patients and help predict resilience during and after the stress of diagnosis and treatment. To improve outcomes for older adults with AML, it will be critical to investigate the predictive utility of patient characteristics in parallel with tumor biology to improve decision-making, inform trial design, and identify actionable targets for supportive care interventions. This review will focus on available data addressing risk assessment for older adults treated for AML with a focus on patient characteristics that may reflect vulnerability to poor treatment tolerance.