We examined the relationship between the cumulative presence of major disease (cancer, stroke, diabetes, heart disease, and hypertension), social support, and self-reported general and emotional well-being in a community representative sample of predominantly White and African American respondents (N = 1349). Across all ages, greater presence of disease predicted poorer reported general health, ... [Show full abstract] and predicted lower emotional well-being for respondents 40 and above. In contrast, social support predicted better-reported general and emotional well-being. We predicted that different types of social support (blood relatives, children, friends, community members) would be relatively more important for health in different age groups based on a lifespan or life stage model. This hypothesis was supported; across all ages, social support was related to better reported general and emotional health, but sources of support differed by age. Broadly, those in younger age groups tended to list familial members as their strongest sources of support, whereas older group members listed their friends and community members. As a whole, social support mediated the effect of disease on reported well-being, however, moderated mediation by type of support was not significant. The results are consistent with a lifespan approach to changing social ties throughout the life course.