This article describes the interplay among theory, research and practice regarding the maintenance of psychological well-being during serious illness. The ideas emerged from two independent lines of work, one that evolved through clinical practice within the medical model, the other that evolved through theory and field research within a behavioral science model. Each of these lines of work independently points to the importance of focusing on psychological well-being and the coping processes that support it, as a complement to the traditional focus in both the medical and behavioral sciences on psychiatric symptoms. This article describes a theoretical framework for the discussion of psychological well-being during serious illness. Then, this framework is used to define variables that research indicates contribute specifically to psychological well-being during serious illness, and finally, based on theory and research, a therapeutic program is described for patients with serious illness. The goal of this paper is to encourage researchers and clinicians to give as much attention to the development and maintenance of psychological well-being in the face of serious illness as they do to the etiology and treatment of psychiatric symptoms. Copyright 2000 John Wiley & Sons, Ltd.