This chapter focuses on the relationship between the psychological response to illness and the development of clinically significant depression. It emphasizes the personal meaning of the illness for the individual, and the associated psychodynamic and cognitive alterations that may lead to depression. Psychological factors determine whether depression results following the onset of a serious medical illness include the capacity of the individual to tolerate the thoughts and feelings that accompany the illness, the ability to integrate the illness into the self-concept and life-plan without an undue fall in self-esteem. The chapter emphasizes how the personal meaning of the illness is influenced by the psychodynamic equilibrium, self-structure, personality, and cognitive disposition of the individual affected. Cognitions defined as "representation(s) of knowledge" or the processes whereby "information is categorized, stored, and integrated with knowledge that is already present". Dysfunctional attitudes include "unrealistic, often perfectionistic, standards by which the self is judged". Cognitive distortions are errors in the processing of information.