Crosstalk between metabolic and immune pathways has recently become appreciated to be key to the regulation of host defence. The hypoxia-inducible factor (HIF) is a transcription factor which was initially described as a ubiquitous master regulator of the transcriptional response to hypoxia. In this role, HIF regulates genes promoting adaptation to hypoxia including a number which influence the cellular metabolic strategy of a cell. It has more recently been appreciated that the regulation of HIF is not restricted to oxygen-dependent pathways, and is now known to be mediated by a number of additional metabolic and immune cues including metabolites and cytokines respectively. Furthermore, our understanding of the functional role of HIF has expanded to it now being appreciated as a major regulator of host immunity. This places HIF in an ideal position to act as a regulatory hub which links metabolic activity with immunity. In this review we synthesise recent data which identifies HIF as both a target and effector for metabolic and immune processes. Developing our understanding of the role of HIF in this context will uncover new therapeutic targets for inflammatory and infectious disease.