The purpose of this article is to discuss conceptual issues surrounding health-related quality of life (HRQOL) and to provide an example of how structural equation modeling can address some of these conceptual issues. This article reports the development of the measurement model for overall quality of life, a dimension of HRQOL as conceptualized by Wilson and Cleary (1995). The sample (N = 1410) is from the AIDS Time-Oriented Health Outcome Study (ATHOS) databank, a longitudinal observational database of persons with HIV-associated illness. The hypothesized second-order factor model consists of 5 latent variables and 17 measured items. The fit indicators (RMSEA = .0717; SRMR = .0450; CFI = .951) suggest that the model provides an adequate description of the pattern of relationships in the data. A theoretical approach to HRQOL will expand its clinical use as an outcome measure and increase its relevance.