Measurement of health-related quality of life is becoming increasingly relevant to controlled clinical trials. Two basic approaches to health-related quality of life measurement are available: generic instruments that attempt to provide a summary of health-related quality of life, and specific instruments that focus on problems associated with individual disease states, patient groups or areas of function. Generic instruments include health profiles and instruments that generate utility measures of health-related quality of life. The approaches are not mutually exclusive. Each approach has its strengths and weaknesses and may be suitable under different circumstances. A number of disease-specific measures for heart failure have been developed. For each measure, there is some evidence regarding key measurement properties, responsiveness and validity. An instrument is responsive if it can detect important changes, even if those changes are small. An instrument is valid if it is really measuring what it is supposed to measure. Only one disease-specific instrument that addresses a wide range of health-related quality of life impairment, the Minnesota Living with Heart Failure Questionnaire, has shown responsiveness in the context of double-blind, multicenter, pharmaceutical clinical trials. Both generic and specific measures should find increasing use in clinical trials in heart failure. Careful attention to rigorous administration is necessary for useful results. Trials should be constructed to obtain additional data regarding both validity and changes in instrument score that correspond to small, medium and large changes in health-related quality of life. If these guidelines are followed, useful information about the impact of interventions on heart failure will become increasingly available.