The management of patients with chronic disease constitutes the largest single cost to the health care system in the United States. New approaches and methods are needed to reduce preventable complications and to enhance the health and well-being of patients with chronic disease and their families. Interventions that target the family setting in which disease management takes place have emerged as an alternative to traditional strategies that focus only on the individual patient or that consider the family only as a peripheral source of positive or negative social support. In this approach, the educational, relational, and personal needs of all family members are emphasized. Data reviewed by the National Working Group on Family-Based Interventions in Chronic Disease identified potential mechanisms by which the relational context of the family affects disease management and how characteristics of family relationships serve as risk or protective factors. In this paper we describe the major forms of family-based interventions, review the results of selected clinical trials, and present applications for clinical practice. The data suggest that approaches to the management of chronic disease should be expanded to include the broader relational context in which disease management takes place. Although it adds complexity to clinical intervention, this approach increases clinical flexibility, addresses the important players in disease management, and accounts for a significant number of risk and protective factors that affect outcome.