In this article the authors review methodological issues that arise when interviews and self-report questionnaires are used with people with mental retardation and offer suggestions for overcoming some of the difficulties described. Examples are drawn from studies that use qualitative methodology, quantitative studies assessing different question types, and studies reporting on the development of instruments measuring psychiatric symptoms, self-concept, and quality of life. Specific problems that arise with respect to item content (e.g., quantitative judgments, generalizations), question phrasing (e.g., modifiers), response format (e.g., acquiescence, multiple-choice questions), and psychometric properties (factor structure and validity) are discussed. It is argued that because many self-report questionnaires include questions that have been found to be problematic in this population, more attention needs to be paid to establishing the validity of such measures and to clearly defining the population for which the instrument is designed.