As the number of chronic diseases is legion, each having a different impact on function and quality of life, our chapter must necessarily be limited in scope. The contents of our chapter are as follows. First, we will introduce the idea that people’s mental models or representations of a chronic disease are shaped by its biological features. Thus, the content of the representation and its similarity with prior illness representations will determine the degree to which the illness is experienced as stressful. Second, although chronic illness as a stressor is similar in many ways to other life stressors, for example job loss, marital discord, and so on, we suggest a specific way in which it differs quantitatively, if not qualitatively, from other stressors. We then review three frameworks or models for viewing and assessing the effects of chronic illness on the individual’s life:(1) the biomedical framework,(2) the stress-coping framework, and (3) a self-regulation framework which describes behavior in the face of chronic illness from the perspective of the sick individual in his or her social and cultural context. We describe each of these approaches and their strengths and weaknesses. Our review of these frameworks highlights three themes. The first is the close connection between the biomedical framework and the self-regulation analysis of adaptation to chronic illness and their sometimes paradoxical differences. The second is the ongoing assimilation and transformation of stress-coping concepts into the self-regulation framework. The third is the recognition of the gaps in empirical study of the processes involved in understanding how the social and cultural context affects the way in which individuals think about, and cope and learn to live with, chronic illness. A further section comments briefly on two topics of special interest to investigators focused on adaptation to chronic illness: adherence to treatment, and emotional responses to chronic illness. Our analysis will elaborate insights into these topics from the perspective of self-regulation theory. The concluding section will summarize the themes that we believe are central to the