Quality-of-life (QOL) instruments used in clinical research can provide important evidence to inform decisions about alternative treatments. This is particularly true when patients, such as those with cancer who are contemplating toxic chemotherapy, face tradeoffs between quantity of life and QOL or when the primary goal of therapy is to improve how patients feel. Surrogate measures (cardiac function, exercise capacity, bone density, tumor size) are inadequate substitutes for direct measurement of QOL. Quality-of-life measures will be most valuable when they comprehensively measure aspects of QOL that are both important to patients and likely to be influenced by therapy, when the QOL measurement instruments are valid (measuring what is intended) and responsive (able to detect all important changes, even if small), and when the results are readily interpretable (determining whether treatment-related changes are trivial, small but important, or large). Researchers are finding new, imaginative ways to help clinicians understand the magnitude of treatment impact on QOL. Additionally, QOL measures may be useful in clinical practice. Recent results from well-designed randomized controlled trials suggest that information on patient QOL provided to clinicians might, in some circumstances, result in benefits for these patients. Further investigation is warranted to confirm these observations and to define the particular combination of methods and settings most likely to yield important benefits.