Intervention research for couples and families managing chronic health problems is in an early developmental stage. We reviewed randomized clinical trials of family interventions for common neurological diseases, cardiovascular diseases, cancer, and diabetes, which is similar to the content of previous reviews discussed later. One overriding theme of these studies is that patients with chronic illnesses and their families face a variety of challenges to which researchers have responded with an array of treatment modalities. Very few of the interventions reviewed, with the exception of treatment for adolescents with diabetes, tested family psychotherapy models. Most interventions were time-limited therapeutic interventions that trained families to improve their communication and problem-solving skills, individual and family coping skills, and medical management. Researchers more clearly described mechanisms of change in intervention studies with cancer and diabetes than with other diseases, and not surprisingly, they found greater empirical support for their interventions. Family interventions show promise to help patients and family members manage chronic illnesses. To develop an empirical base for family approaches to managing chronic illnesses, interventions must be based on theories that delineate mechanisms of change in family processes and skills in medical management necessary to maintain patients’ and family members’ health.