The current biomedical and psychosocial frameworks that form the conceptual basis of medicine today are insufficient to address the needs of the medically complex and environmentally challenged populations of patients often cared for by physical medicine and rehabilitation specialists. The expanded biopsycho-ecological model of health, illness, injury, and disability operating through mechanisms of Health Environmental Integration (HEI) encourages a more complete understanding of illness, injury, activity limitation, and participation restriction as arising at the interface between the person and the environment. HEI recognizes complex interacting multilevel functional hierarchies beginning at the cellular level and ending at the individual’s experience of the environment. Although the foci of illness and injury are within the body and mind, the physical and social environments contain elements that can cause or exacerbate disease and barriers that interact in ways that lead to injuries and disabilities. Furthermore, these environments hold the elements from which treating agents, facilitators, and social supports must be fashioned. The highly integrative biopsycho-ecological framework provides an expanded basis for understanding the objective causes and subjective meanings of disabilities. Disabilities are reduced through HEI by seeking to maximally integrate the body and mind (the self) with both the surrounding physical environment and other people in society. HEI offers mechanisms for interdisciplinary research, an expanded framework for education and empowerment, and a blueprint for optimizing day-to-day clinical care at both the individual patient and treatment population levels in the ever-changing scientific, political, and policy environments.