Myeloid cells are key effectors of the innate immune response, and as such are often required to migrate to, and function within, sites that are markedly hypoxic. To adapt to such oxygen deplete environments they have developed functional and survival responses that are regulated by the hypoxia-inducible factor (HIF) oxygen-sensing pathway. In this review, we describe three key aspects of HIF-dependent regulation of myeloid cell function: (i) the maintenance of ATP pools and the subsequent regulation of proinflammatory responses, (ii) the HIF-dependent inhibition of neutrophil apoptosis and (iii) the HIF-mediated regulation beta2 integrin expression.