Background: Personality functioning, also referred to as structural integration, describes basic emotion-related perception and regulation capacities directed towards the self and others. Patients with impairments of personality functioning experience difficulties in self-regulation and interpersonal relations. Although personality functioning has become increasingly important in psychotherapeutic and psychiatric diagnoses and treatment planning, there is little systematic evidence on the role of personality functioning in patients with chronic and somatic diseases. This article reviews empirical studies using standardized assessments of personality functioning in patients with chronic and somatic diseases and discusses the role of personality structure in psychosomatic medicine. Results: Currently, there are only a limited number of studies using standardized assessments of personality functioning in patients with chronic or somatic diseases. The available evidence points to correlations of personality functioning with pain perception and the development of chronic pain. In addition, patients with lower levels of personality functioning may have difficulties in managing chronic conditions that require enduring changes in health behavior, such as in diabetes or posttransplantation therapy. Conclusion: The review suggests a systematic link between personality functioning and health behavior in patients with chronic diseases that relate to self-regulation and coping strategies. These findings underline the importance of assessing personality functioning for diagnostics and treatment planning in psychosomatic medicine. Finally, an assessment of personality functioning could be helpful in choosing specific psychotherapeutic treatment strategies; however, more empirical studies are needed to comprehensively prove these assumptions.