While measurement of quality of life is a vital part of assessing the effect of treatment in many clinical trials, a measure that is responsive to clinically important change is often unavailable. Investigators are therefore faced with the challenge of constructing an index for a specific condition or even for a single trial. There are several stages in the development and testing of a quality-of-life measure: selecting an initial item pool, choosing the "best" items from that pool, deciding on questionnaire format, pre-testing the instrument, and demonstrating the responsiveness and validity of the instrument. At each stage the investigator must choose between a rigorous, time-consuming approach to questionnaire construction that will establish the clinical relevance, responsiveness and validity of the instrument and a more efficient, less costly strategy that leaves reproducibility, responsiveness and validity untested. This article describes these options and outlines a pragmatic approach that yields consistently satisfactory disease-specific measures of quality of life.