Hypoxia and inflammation are co-incidental events in an array of diseased tissues including chronically inflamed sites (e.g. Inflammatory Bowel Disease, Rheumatoid Arthritis), growing tumors, myocardial infarcts, atherosclerotic plaques, healing wounds and sites of bacterial infection. Cells have evolved the ability to adapt to hypoxia through the induction of a specific transcriptional pathway governed by the hypoxia inducible factor-1 (HIF-1) which regulates the expression of genes promoting angiogenesis, vasodilatation, glycolysis and erythropoesis. The induction of such genes leads to increased tissue perfusion and anaerobic metabolism thus maintaining ATP levels. As well as a primary role in this adaptive response, HIF-1 also appears to play an important role in the control of inflammatory processes. Hypoxia also activates NF?appaB, a critical transcription factor in the promotion and progression of inflammatory and anti-apoptotic processes. However, the mechanism by which hypoxia activates NF?appaB and thus contributes to inflammation via this pathway has until recently remained elusive. A greater understanding of the oxygen sensing and signalling pathways leading to the activation of these important transcriptional regulators is critical in the identification of new windows of therapeutic opportunity in a diverse range of pathological processes where hypoxia and inflammation co-exist.