The evolution of genomic science and its effect on medicine and health care offer opportunities for family therapists to participate in the comprehensive care of patients and families with genetic disorders. This article provides an overview of what we now know about the psychological and interpersonal experience of patients and families facing some of these illnesses. Case examples illustrate the process of decision-making about testing and treatment, and the importance of understanding developmental issues and transgenerational family dynamics in any related psychotherapy. Challenging emotional issues include managing anger, ambivalence, and guilt; challenging interpersonal issues include dealing with differing coping and communication styles, decisions about disclosure and secrets, and conflict resolution. Family-oriented interventions include individual, couple, and family therapy, and psychoeducational groups. Recommendations are made for family therapists to participate as part of the genetic healthcare team.