Insulin secretion must be tightly coupled to nutritional state to maintain blood glucose homeostasis. To this end, pancreatic β‐cells sense and respond to changes in metabolic conditions, thereby anticipating insulin demands for a given physiological context. This is achieved in part through adjustments of nutrient metabolism, which is controlled at several levels including allosteric regulation, post‐translational modifications, and altered expression of metabolic enzymes. In this review, we discuss mechanisms of β‐cell metabolic and functional adaptation in the context of two physiological states that alter glucose‐stimulated insulin secretion: fasting and insulin resistance. We review current knowledge of metabolic changes that occur in the β‐cell during adaptation and specifically discuss transcriptional mechanisms that underlie β‐cell adaptation. A more comprehensive understanding of how β‐cells adapt to changes in nutrient state could identify mechanisms to be co‐opted for therapeutically modulating insulin secretion in metabolic disease.