Accumulating evidence shows how diverse physiological functions, such as metabolism, immunity, tissue homeostasis, and hematopoiesis, are intricately and profoundly intertwined at multiple levels. This brief review will present evidence from a rapidly expanding field of immunometabolism, highlighting how cells that are relevant to processes at play in determining vascular health and disease can be programmed by changes in their metabolic environment. It will focus on how such changes can be imprinted or trained, particularly through epigenetic modifications, such that adaptations driven by metabolic signals can cause persistent changes in cell function, even after the original stimulus has been corrected or removed. Recognition of these processes and elucidation of the mechanisms underlying them stand to have far-reaching implications for the diagnosis and treatment of diabetes and related metabolic states.