Four generic, preference-weighted, health-related quality of life (HRQL) questionnaires (the Quality of Well-Being, the Health Utilities Index, the EQ-5D, and the SF-6D) are reviewed. Although all of these questionnaires are designed to measure the same concept, each uses a different model of health, a different method of deriving preferences, and a different scoring formula. Head-to-head comparisons of preference-weighted questionnaires are limited. By considering several hypothetical health states, we found that utility scores for equivalent states can vary substantially, depending on the measure used. Clinicians and researchers applying preference-weighted HRQL questionnaires should be aware of such differences and exercise caution when interpreting the results.