This chapter outlines the value of patient-reported outcome (PRO) questionnaires to our understanding of the impact of disease. It summarizes the different types of PROs, their required scaling and psychometric properties and their development. The most common PRO constructs used in clinical studies are measures of impairment (symptoms), activity limitations (functioning), participation restrictions, health status/health-related quality of life, quality of life, and treatment satisfaction. Underlying the quality of PROs is the need for a clear theoretical underpinning and the application of modern statistical techniques in their development - among which is the application of item response theory - especially the Rasch models. The development of new health-related items for Rasch models requires two fundamental processes: consideration of measurement issues and questionnaire development.