The integration of established and emerging digital technologies into the institutions and activities of daily life produces important digital transformations that have profound impacts on health and well-being. In this Perspective, we articulate the urgent need for close attention to the health-related impacts of the diverse uses of digital technologies and the transformations they bring about on a global scale. We provide a conceptual summary of definitions of the Digital Determinants of Health published in the peer-reviewed literature and present progress toward a conceptual framework for understanding the Digital Determinants of Health as operating through primary (individual and community health), secondary (domestic institutions), and tertiary (global political economy) mechanisms. We call for dialogue and collaboration to deepen work on the Digital Determinants of Health for more just and equitable impacts of digital transformations for global population health.