ABSTRACT Support is requested for a Keystone Symposia conference entitled Metabolic Decisions in Development and Disease, organized by Drs. Irene Miguel-Aliaga, Ralph J. DeBerardinis and A.J. Marian Walhout. The conference will be part of Keystone Symposia’s eSymposia Conference Series, which are virtual events. The dates for this online conference will be March 21-24, 2021. Metabolism was once regarded as a homeostatic, housekeeping process that supported but did not instruct cell signaling, gene expression and other networks. In recent years, it has become apparent that metabolism is intimately intertwined with many other networks that determine cellular fate and tissue function, and that metabolites can transmit signals within and between cells. The impact of metabolic signaling is illustrated by the consequences of its dysregulation and it is now understood that many diseases involve pathologically altered metabolism. Mutations in metabolic enzymes underlie numerous developmental disorders, and metabolic alterations in malignant cells impair cellular differentiation and fuel tumor growth. These observations have rekindled interest in disease-oriented metabolism research, which now benefits from increasingly sophisticated analytical and computational tools to understand metabolism and to localize important activities in space and time. The unifying theme of this conference is that proper development requires exquisite metabolic control, and that perturbed metabolism can result in developmental diseases. The conference will bring together scientists exploring how metabolites impact cellular and developmental decisions in a diverse range of model systems, and mechanisms underlying developmental disorders caused by aberrant metabolism. Topics will include the epigenetic roles of metabolites and their oncogenic potential, signaling roles of metabolites across organs, metabolic control of development, and the impact of microbiota- mediated signaling in ageing and metabolic disease. Collectively, participants attending this conference will foster collaborations across a range of disciplines, provide biological questions for emerging technologies, and ultimately develop a new conceptual framework for the study of the instructive roles of metabolites in biology and disease. This novel conference program is designed to capitalize on both the technological and conceptual momentum of this budding field.