This handbook signals a paradigm shift in health research. Population-based disciplines have employed large national samples to examine how sociodemographic factors contour rates of morbidity and mortality. Behavioral and psychosocial disciplines have studied the factors that influence these domains using small, nonrepresentative samples in experimental or longitudinal contexts. Biomedical disciplines, drawing on diverse fields, have examined mechanistic processes implicated in disease outcomes. The collection of chapters in this handbook embraces all such prior approaches and, via targeted questions, illustrates how they can be woven together. Diverse contributions showcase how social structural influences work together with psychosocial influences or experiential factors to impact differing health outcomes, including profiles of biological risk across distinct physiological systems. These varied biopsychosocial advances have grown up around the Midlife in the United States (MIDUS) national study of health, begun over 20 years ago and now encompassing over 12,000 Americans followed through time. The overarching principle behind the MIDUS enterprise is that deeper understanding of why some individuals remain healthy and well as they move across the decades of adult life, while others succumb to differing varieties of disease, dysfunction, or disability, requires a commitment to comprehensiveness that attends to the interplay of multiple interacting influences. Put another way, all of the disciplines mentioned have reliably documented influences on health, but in and of themselves, each is inherently limited because it neglects factors known to matter for health outside the discipline’s purview. Integrative health science is the alternative seeking to overcome these limitations.