Volatile anaesthetics induce early and late preconditioning in several organs, including the heart. This phenomenon is of particular interest in the clinical setting to reduce infarct size and to elicit adaptive functions of the heart. One possible mechanism of anaesthetic-induced preconditioning is the activation of the transcription factor hypoxia-inducible factor 1alpha (HIF-1alpha) and its target gene responses. It was shown that pharmacological activation of the hypoxia-inducible factor 1alpha pathway is organ protective, and recent studies demonstrated that isoflurane and xenon lead to hypoxia-inducible factor 1alpha upregulation, which is related to the preconditioning effect of the inhalational anaesthetics. A better understanding of the molecular mechanisms that mediate cardioprotection by volatile anaesthetics might help to introduce specific applications of these substances for organ-protective purposes in patients with cardiovascular diseases.