During the past two decades, the public health community’s attention has been drawn increasingly to the social determinants of health (SDH)—the factors apart from medical care that can be influenced by social policies and shape health in powerful ways. We use “medical care” rather than “health care” to refer to clinical services, to avoid potential confusion between “health” and “health care.” The World Health Organization’s Commission on the Social Determinants of Health has defined SDH as “the conditions in which people are born, grow, live, work and age” and “the fundamental drivers of these conditions.” The term “social determinants” often evokes factors such as health-related features of neighborhoods (e g., walkability, recreational areas, and accessibility of healthful foods), which can influence health-related behaviors. Evidence has accumulated, however, pointing to socioeconomic factors such as income, wealth, and education as the fundamental causes of a wide range of health outcomes This article broadly reviews some of the knowledge accumulated to date that highlights the importance of social—and particularly socioeconomic—factors in shaping health, and plausible pathways and biological mechanisms that may explain their effects. We also discuss challenges to advancing this knowledge and how they might be overcome.