Dramatic global-migration patterns over recent decades have forever changed the racial, ethnic, social, and cultural makeup of the people of the United States. Simultaneously, the patterns of disease and risk factor distribution within the U.S. population are changing in ways that accentuate the role of lifestyle, behavior, and social and economic differences in the onset and outcomes of disease. Medical school curricula must prepare students to address these demographic realities. The University of California, San Francisco’s (UCSF’s) redesigned curriculum, launched in September 2001, integrates social, behavioral, and biomedical science education in an early and sustained way. The traditional undergraduate medical structure of two years of basic science plus two years of clinical rotations was replaced with a model divided into three stages spanning four years: the Essential Core, the Clinical Core, and Advanced Studies. The authors summarize the role of the social and behavioral sciences in the UCSF Essential Core—the first 16 months of instruction divided into integrated blocks, each centered on clinical cases. Basic thematic areas (e.g., behavior change, health disparities), content illustrations (e.g., Introduction to the Biopsychosocial Model, The Culture of Medicine), and process considerations (e.g., integration, content order, evaluations) are presented. Special challenges and limitations are also discussed.