There is wide recognition that cultural models influence how individuals interpret the signs and symptoms of illness, including psychiatric disorders. The processes of interpreting and ascribing meaning to one's bodily sensations, thoughts, feelings and behaviour are mediated by cognitive models and social interactions with others, which in turn reflect cultural knowledge and practices. Social scientists have distinguished between the biomedical concept of disease, the patient's subjective experience of illness, and the social meanings of sickness, eachof which may be based on different explanatory models [1, 2]. However, pathophysiology, individual psychology and social responses interact. The cultural mediation of illness meaning, therefore, not only shapes the social manifestations of distress through symptom reports and help-seeking, but also influences the underlying psychophysiological processes that contribute to psychopathology and illness experience. In this chapter, we provide some examples of how social context and explanatory models influence common psychiatric conditions, including somatization, dissociation, mood, and anxiety disorders, as well as psychotic experience. Our aim is to demonstrate the important role played by explanations in the mechanisms of psychopathology as well as in clinical illness behaviour. Explanatory models are therefore an important target of research, clinical assessment, and intervention.Psychiatric Diagnosis: Challenges and Prospects Edited by Ihsan M. Salloum and Juan E. Mezzich