Whilst neutrophils are required for an effective host pathogen response, inappropriate or persistent neutrophilic inflammation is also associated with a number of disease states exemplified by acute lung injury responses and chronic obstructive pulmonary disease. Tight regulation of neutrophil function and survival in the tissues is therefore important in maintaining a balance that benefits the host. During the inflammatory response, tissue environments are frequently characterised by limited oxygen and nutrient availability. We, and others, have described that local and systemic hypoxia is a critical component of the inflammatory response, with oxygen-sensing pathways implicated in the regulation of neutrophil survival. In this talk I will explore how the adaptation of neutrophils to sites of tissue injury and infection is driven by interplay between oxygen and metabolite sensing pathways. The ability to reprogram neutrophil metabolism by hypoxia and activation of the HIF response will also be discussed in the context of acute bacterial challenge. Finally, the therapeutic potential of targeting hypoxia signalling pathways will be considered for the treatment of inflammatory lung disease.