OBJECTIVE: The present article presents an overview of theoretical constructs and mechanisms of health behavior change that have been found useful in research on people with chronic illness and disability. A self-regulation framework (Health Action Process Approach) serves as a backdrop, making a distinction between goal setting and goal pursuit. Risk perception, outcome expectancies, and task self-efficacy are seen as predisposing factors in the goal-setting (motivational) phase, whereas planning, action control, and maintenance/recovery self-efficacy are regarded as being influential in the subsequent goal-pursuit (volitional) phase. The first phase leads to forming an intention, and the second to actual behavior change. Such a mediator model serves to explain social-cognitive processes in health behavior change. By adding a second layer, a moderator model is provided in which three stages are distinguished to segment the audience for tailored interventions. Identifying persons as preintenders, intenders, or actors offers an opportunity to match theory-based treatments to specific target groups. Numerous research and assessment examples, especially within the physical activity domain, serve to illustrate the application of the model to rehabilitation settings and health promotion for people with chronic illness or disability. CONCLUSIONS/IMPLICATIONS: The theoretical developments and research evidence for the self-regulation framework explain the cognitive mechanisms of behavior change and adherence to treatment in the rehabilitation setting.