Uncertainty is a pervasive and important problem that has attracted increasing attention in health care, given the growing emphasis on evidence-based medicine, shared decision making, and patient-centered care. However, our understanding of this problem is limited, in part because of the absence of a unified, coherent concept of uncertainty. There are multiple meanings and varieties of uncertainty in health care that are not often distinguished or acknowledged although each may have unique effects or warrant different courses of action. The literature on uncertainty in health care is thus fragmented, and existing insights have been incompletely translated to clinical practice. This article addresses this problem by synthesizing diverse theoretical and empirical literature from the fields of communication, decision science, engineering, health services research, and psychology and developing a new integrative conceptual taxonomy of uncertainty. A 3-dimensional taxonomy is proposed that characterizes uncertainty in health care according to its fundamental sources, issues, and locus. It is shown how this new taxonomy facilitates an organized approach to the problem of uncertainty in health care by clarifying its nature and prognosis and suggesting appropriate strategies for its analysis and management.