AIMS: To develop an explanatory framework concerning patient experience of diabetes and depression and the relationship between these disorders; to better understand how interventions and health services should be delivered for this group of patients. METHODS: The study used meta-synthesis. Published qualitative studies were identified using a structured search, and themes synthesized across studies to develop a new explanatory framework. RESULTS: Searches of three databases identified 5506 papers, and 22 were included. Diagnosis of diabetes and the impact of symptoms on functioning were associated with varied psychological reactions, not all of which are negative, and the concept of 'depression' only captures aspects of the experience. Similarly, the relationship between diabetes and relationships with professionals and family were variable, with relationships serving as both a buffer of the effects of diabetes and potentially as a cause of further difficulties for patients. Depression and other psychological states were significant barriers to effective coping. Definition of 'self' emerged as a key potential moderator of the relationship between depression and diabetes. CONCLUSIONS: The variability in psychological reactions to diabetes suggested three key clinical implications, reflecting increasing levels of complexity for practitioners.