Uncertainty is widely believed to be a central feature in illness experiences. Moreover, communication is thought to be essential to the construction, management, and resolution of uncertainty. Not surprisingly, however, there are substantial variations in conceptions and analyses of this focal construct and its relation to communication. In this article, we first argue that understandings of the role of communication in health and illness can be improved substantially--thereby enhancing both theory development and practical applications of health communication theory--by recognizing and reconciling sources of variation in conceptions of uncertainty and by synthesizing various specific conceptions. We then review individual-psychological models. linguistic and discourse analyses, and sociocultural and historical perspectives on uncertainty in illness Following the review, we present a framework that synthesizes many conceptions of uncertainty We close with a discussion of 5 challenges and opportunities for research and application.