The theory of ambiguous loss is applied to chronic illness in individuals, couples, and families. Lack of clarity about prognosis, daily physical condition, and fluctuating capabilities create relationship confusion, preoccupation with the illness, or avoidance of the ill individual. Immobilization, depression, and relationship collapse may occur in response to features of chronic illness over which there is no control. A case study illustrates helpful therapeutic interventions for couples and families with chronically ill members. © 2002 Wiley Periodicals, Inc. J Clin Psychol/In Session 58: 1351–1360, 2002.