<p>Health-related quality of life (HRQOL) and daily functioning are central considerations for older adults with cancer. Attention to symptom burden, daily functioning, and HRQOL is imperative in this patient population to identify relevant research endpoints and outcomes and to provide care that matches individual needs. Patient-reported outcomes (PROs) are an indispensable source of information about the effects of disease and treatment on patient wellbeing. Integrating PROs with comprehensive geriatric assessment (CGA), which targets medical, psychosocial, and functional-impairment vulnerabilities, is key to identifying patients who need supportive measures. However, patient-related factors (e.g., decline, survival, satisfaction with life, coping, and intervention effects) present measurement challenges, with implications for research and practice. As patients age, the severity of age-related impairments will undoubtedly increase, profoundly and negatively affecting HRQOL and physical functioning. Because HRQOL in the elderly is a complex concept, measuring it can be challenging. Existing measures typically assess HRQOL as functional health, adverse symptoms, and global quality of life—capturing only a portion of this complex concept, with potentially less consideration of the effects of age-related deterioration on functioning dimensions. Moreover, older adults with cancer are underrepresented in randomized clinical trials, and the completeness of PRO reporting by older adults is often suboptimal. Further studies are thus needed to validate PROs and CGA in this population and define the minimum clinically important difference to use in RCTs for these patients. Future efforts should focus on maximizing the use of CGA and appropriate PROs among aged patients to improve geriatric oncology care and to establish clinical benefit in anticancer trials in these patients.</p>