This is the sixth article in a series intended to summarize the state of the science for assessing the clinical significance of quality-of-life (QOL) assessments. The previous 5 articles dealt with specific methodological issues, whereas this article addresses practical considerations in implementing the methods and presenting the results to various audiences with differing perspectives. Proposals for how to interpret the “clinical significance” or “clinical meaningfulness” of changes in QOL scores were addressed in previous articles within this series. Within this article, 4 audiences—patients and physicians, clinical researchers, health policymakers, and private- and public-sector employees who work in health-related fields—are examined because each is a unique stakeholder with a distinct vantage point and each can interpret QOL outcomes differently. A clinician may attempt to explain to a patient potential treatment alternatives for his or her QOL; a health policymaker may try to describe to elected officials the financial impact on a patient population with reduced QOL; a researcher may try to obtain the vital messages from a clinical trial that included QOL end points; and a regulatory agency and/or pharmaceutical company may try to ascertain the appropriate level of evidence required for a successful research study. For each of the 4 audiences, concrete examples and practical guidelines are offered by which changes in QOL outcomes can be interpreted meaningfully. Ultimately, both determining and disseminating the meaning of clinical significance are functions of the outlook of the audience because the perspective of the audience determines its ability to comprehend, evaluate, and convey the context within which such outcomes appear meaningful. Among the audiences described within this article, a commonality of interests exist that mandates a careful exposition of the scientific rigor involved in describing the clinical significance of QOL assessments. Collectively, this series attempts to provide methods and means for making such determinations.