From bacteria to mammals, ambient O2 tension influences such diverse cellular functions as gene expression, secretion, contraction and the patterns of electrical activity. Some of the effects of O2 are attributed to its interaction with various classes of voltage-dependent ion channels. In glomus cells of the carotid body, the differential properties of O2-sensitive K+ and Ca2+ channels help us to understand the basic features of O2 chemoreception. Modifications of ion-channel activity in response to changes in the partial pressure of O2 are also involved in the adjustments of vascular tone to hypoxia as well as in the response of chemoreceptors in pulmonary airways. Direct O2-sensing by ion channels might also help to explain the alterations of brain function by low O2 tension. The O2-sensitivity of ion-channel activity appears to be a broadly distributed phenomenon contributing to a wide variety of cellular responses to hypoxia.