Epidemiology has long been central to public health, guiding our understanding of the distribution and determinants of disease. As the field has evolved—from John Snow’s cholera investigations to large-scale cohort studies and causal inference frameworks—it now faces a transformative juncture with the advent of artificial intelligence/machine learning (AI/ML). These technologies offer unprecedented opportunities to improve data measurement, inference, and population health insights, yet also pose methodological and ethical challenges. Anchored by the core epidemiologic domains of study population, measurement, and inference, we examine how epidemiologists can use AI/ML effectively. We consider the importance of careful population definition, informed sampling, and external validation to ensure generalizability and minimize bias when AI/ML is used. We also explore the need for rigorous assessment of data quality and model reliability, which strengthens the case for conceptual frameworks in guiding interpretation of scientific investigations. To realize AI/ML’s potential, epidemiology must adapt its training, invest in infrastructure, and promote interdisciplinary collaboration. Doing so will ensure that epidemiologic science remains robust, reproducible, and relevant in a rapidly evolving informational landscape. This moment calls for a strategic integration of AI/ML into the fabric of epidemiologic practice and training to advance both science and public health.