When faced with the uncertainty of serious illness, individuals cope by comparing themselves to other people (social comparisons) and to other times in their lives (temporal comparisons). Participants were 44 individuals being treated for HIV who completed questionnaires measuring comparisons, adherence, and self-efficacy; 34 also completed qualitative interviews that were coded for comparisons. High levels of comparison to worse-off others, worse-off past selves, and better-off future selves were prevalent. Comparisons to worse-off others resulting in positive affect were associated with greater medication adherence; comparisons to better-off others resulting in negative affect were related to worse adherence. Self-efficacy to adhere mediated the relationship between comparison and adherence. Individuals who are uncertain about treatment outcomes may engage in social comparison to gain specific knowledge about adherence.