Do the meanings inherent within a traumatic life event increase our understanding of differential mental health outcomes? In light of this question two central issues are addressed in this article: (1) what variables influence the meaning that is constructed in response to a crisis, and (2) how does this meaning affect the self and ultimately the adaptation/mental health outcome as indicated by the level of emotional distress? A theoretical model is evaluated via a comparative analysis that incorporates the data of 76 persons with cancer and 130 persons with HIV/AIDS. Three primary findings support this model and the significance of the role of meaning in response to a crisis: (1) the meaning constructed in response to a crisis can be operationalized and its role evaluated as a dimension of the adaptation process, (2) evidence indicates constructed meaning affects self-perception, which subsequently affects adaptation, and (3) the pattern of effects does not differ by illness type since analyses indicate meaning is central to individuals' responses regardless of differences in characteristics of the event.