We extended Wilson and Cleary's (1995) health-related quality of life model to examine the relationships among symptom status (Symptoms), functional health (Disability), and quality of life (QOL). Using a community sample (N = 956) of male HIV positive patients, we tested a mediation model in which the relationship between Symptoms and QOL is partially mediated by Disability. Common and unique ideas from 3 approaches to examining moderation of effects in mediational models (Edwards & Lambert, 2007; MacKinnon, 2008; Preacher, Rucker, & Hayes, 2007) were used to test whether (a) the direct relationship of Symptoms to QOL and (b) the relationship of Disability to QOL are moderated by age. In the mediation model, both the direct and the indirect (mediated) effects were significant. The direct relationship of Symptoms to QOL was significantly moderated by age, but the relationship of Disability to QOL was not. High Symptoms were associated with lower QOL at all ages, but this relationship became stronger at older ages. We compare the 3 approaches and consider their advantages over traditional approaches to combining mediation and moderation. (Contains 4 figures, 1 table, and 4 footnotes.)