Perseverative cognition (PC), such as worry and rumination, is a common reaction to stressful events in everyday life. According to the PC hypothesis, prolonged cognitive representations of stressful events will increase the total amount of time that these events have a “wear and tear” effect on the human body. In this chapter, we provide an overview of the role that PC plays in the onset and maintenance of stress related mental and somatic health problems. Furthermore, we propose that unconscious PC, traditionally studied within the context of psychopathology, might have substantial somatic health relevant effects as well. Finally, we present a self-regulation perspective on PC and propose that it forms part of the default response to threat, novelty and ambiguity. This default response is enhanced in chronic worriers who show excessive commitment to their goals, use PC as a strategy to cope with possible threats to goal attainment and have difficulties to recognize signals of safety. In conclusion, research on the PC hypothesis has provided valuable insight into the link between stressful events, psychopathology, and somatic health.