Comorbidity is associated with worse health outcomes, more complex clinical management, and increased health care costs. There is no agreement, however, on the meaning of the term, and related constructs, such as multimorbidity, morbidity burden, and patient complexity, are not well conceptualized. In this article, we review definitions of comorbidity and their relationship to related constructs. We show that the value of a given construct lies in its ability to explain a particular phenomenon of interest within the domains of (1) clinical care, (2) epidemiology, or (3) health services planning and financing. Mechanisms that may underlie the coexistence of 2 or more conditions in a patient (direct causation, associated risk factors, heterogeneity, independence) are examined, and the implications for clinical care considered. We conclude that the more precise use of constructs, as proposed in this article, would lead to improved research into the phenomenon of ill health in clinical care, epidemiology, and health services.