Older adults with cancer constitute a heterogeneous group of patients who pose unique challenges for oncology care. One major concern is how to identify patients who are at a higher risk for chemotherapy intolerance, because a standard oncology workup may not always be able to distinguish an older individual’s level of risk for treatment-related complications. Geriatric oncologists incorporate tools used in the field of geriatrics, and have developed the Comprehensive Geriatric Assessment to enhance the standard oncology workup. This assessment pinpoints problems with daily activities, comorbidities, medications, nutritional status, cognitive function, psychological state, and social support systems, all of which are risk factors for treatment vulnerability in older adults with cancer. Additional tools that also serve to predict chemotherapy toxicity in older patients with cancer are now available to identify patients at higher risk for morbidity and mortality. Together, these instruments complement the standard oncology workup by providing a global assessment, thereby guiding therapeutic interventions that may improve a patient’s quality of life and clinical outcomes.