Arousal from sleep in response to CO₂ is a life‐preserving reflex that enhances ventilatory drive and facilitates behavioural adaptations to restore eupnoeic breathing. Recurrent activation of the CO₂‐arousal reflex is associated with sleep disruption in obstructive sleep apnoea. In this review we examine the role of chemoreceptors in the carotid bodies, the retrotrapezoid nucleus and serotonergic neurons in the dorsal raphe in the CO₂‐arousal reflex. We also provide an overview of the supra‐medullary structures that mediate CO₂‐induced arousal. We propose a framework for the CO₂‐arousal reflex in which the activity of the chemoreceptors converges in the parabrachial nucleus to trigger cortical arousal.