<p>Cognitive impairment is associated with perturbations of fine-tuned neuroimmune interactions. At the molecular level, alterations in cellular metabolism can compromise brain function, driving structural damage and cognitive deficits. In this Review, we focus on the bidirectional interactions between microglia, the brain-resident immune cells and neurons to dissect the metabolic determinants of brain resilience and cognition. We first outline these metabolic pathways during development and adult life. Then, we delineate how these processes are perturbed in ageing, as well as in metabolic, neuroinflammatory and neurodegenerative disorders. By doing so, we provide a mechanistic understanding of the metabolic pathways relevant to cognitive function in health and disease, thus paving the way for novel therapeutic targets based on the emerging field of neuroimmunometabolism.</p>