Considerable progress has been made over the past 2 decades in defining and measuring health-related quality of life (QOL), and there is a growing recognition that these measures provide unique information about the impact of a chronic illness and its treatment. For patients with cystic fibrosis (CF), health-related QOL measures enable researchers and clinicians to determine the effects of clinical interventions on several aspects of daily living (psychological, emotional, social) that are not reflected in typical health indicators, eg, pulmonary functioning scores. Three types of health-related QOL measures have been developed: 1) utility measures, 2) health profiles, and 3) disease-specific measures. The purpose of each type of health-related QOL measure is described, and its application to patients with CF is reviewed. Although important descriptive information has been obtained from utility measures, eg, the Quality of Well-Being Scale, and health profiles, eg, the Nottingham Health Profile, both of these instruments have serious limitations. Disease-specific measures, similar to those developed for children and adults with asthma, seem to hold the greatest promise for advancing our understanding of the impact of CF on daily life and for evaluating the effectiveness of new clinical interventions. The Cystic Fibrosis Questionnaire is the only published disease-specific measure of health-related QOL for children, adolescents, and adults with CF. Its psychometric properties are briefly reviewed, and directions for future research are suggested.