Nitric oxide (NO) is a versatile molecule that plays key roles in the development and survival of mammalian species by endowing brain neuronal networks with the ability to make continual adjustments to function in response to moment-to-moment changes in physiological input. Here, we summarize the progress in the field and argue that NO-synthetizing neurons and NO signalling in the brain provide a core hub for integrating sensory- and homeostatic-related cues, control key bodily functions, and provide a potential target for new therapeutic opportunities against several neuroendocrine and behavioural abnormalities.