Abstract Objective Illness intrusiveness is a common, underlying determinant of quality of life in people affected by chronic disease. Illness intrusiveness results from disease- and treatment-induced disruptions to lifestyles, activities, and interests (i.e., interference with psychologically meaningful activity). This paper introduces the Illness Intrusiveness Ratings Scale (IIRS), a 13-item, self-report instrument. The IIRS can be scored to generate a total score or three subscale scores: relationships and personal development, intimacy, and instrumental. In addition to describing the IIRS, the paper presents the theoretical framework in which it is anchored, reviews the evidence, and reports psychometric properties. Methods Qualitative literature review. Results Findings support the IIRS's reliability (internal consistency and test–retest), validity (construct, criterion-related, and discriminant), sensitivity to change, and factorial invariance across numerous chronic-disease groups. The paper reports IIRS reliability coefficients and normative statistics for 36 chronic, medical and psychiatric patient populations. Conclusion The IIRS taps the extent to which disease- and treatment-related factors interfere with psychologically meaningful activity among people affected by chronic disease. It provides a valid, reliable measure that is easy to administer and unequivocally interpretable rendering it suitable for research designed to estimate the psychosocial impact of chronic disease and to document (and compare) the effectiveness of therapeutic interventions.