The present review describes the clinical utility of a research-informed Family Systems-Illness model and a family resilience framework in helping families meet the challenges of child and adolescent illness, disability, and loss. Together they provide a psychosocial map to guide families through the illness experience over time and to facilitate effective coping and adaptation, thereby enhancing the quality of life for children and their families. Key processes and intervention guidelines of this strengths-oriented, collaborative approach are outlined, with attention to multigenerational, life cycle, and socio-cultural influences.A growing body of research on resilience finds that family resources are significant influences in positive adaptation to adversity, such as a major health problem. Research also demonstrates the impact of serious illness on families across the life cycle and the relationship of family dynamics to illness behavior, adherence, and disease course.The Family Resilience and Family Systems-Illness models offer a framework for collaborative practice to foster optimal coping and adaptation to chronic child and adolescent illness or disability.