A large part of contemporary medicine is concerned with describing and understanding the biological mechanisms involved in disease causation. Comparatively less attention has been paid to the socioeconomic and behavioral mechanisms underlying disease. This article argues for an integration of social, behavioral, and biological factors in the explanation of pathogenesis, a perspective that is in accord with the vision of pioneer public health practitioners of the 19th century, but that has gradually been overtaken by the dominance of the biomedical disease model. In recent decades, the social components of disease have been depicted as “distal” factors or used as “classificatory” devices. We explain how the integration we propose, which draws upon the concepts of “mixed mechanism” and of “lifeworld,” advances the view of several scholars of the recent past. Finally, we discuss new findings in epigenetics and psychology, where socioeconomic disparities appear to be an integral part of the explanation of health conditions, to illustrate how the integration may work in practice.