Measurement of health-related quality of life (HRQOL) in people with disability can be problematic. Ambiguous or paradoxical findings can occur because of differences among people or changes within people regarding internal standards, values, or conceptualization of HRQOL. These "response shifts" can affect standard psychometric indices, such as reliability and validity. Attending to appraisal processes and response shift theory can inform development of HRQOL measures for people with disability that do not confound function and health and that consider important causal indicators such as environment. By design, most HRQOL measures equate function with health, necessarily leading to a lower measured HRQOL in people with functional impairments regardless of their level of self-perceived health. In this article, we present theoretical and conceptual distinctions building on response shift theory and other current developments in HRQOL research. We then submit a set of suggested directions for future measurement development in populations with disabilities that consider these distinctions and extend their use in future measurement developments.