The oxygen sensitive transcription factor hypoxia inducible factor-1 (HIF-1) is known as the key regulator of hypoxia induced gene expression. The microenvironment of inflamed and injured tissue is characterized by low levels of oxygen and glucose and high levels of inflammatory cytokines, reactive oxygen and metabolites. In addition to hypoxia, a broad variety of inflammatory mediators like the proinflammatory cytokines IL-1-beta and TNF-alpha, as well as bacterial lipopolysaccharides (LPS) have been shown to induce HIF-1 suggesting an integrative role for HIF-1 in conditions of hypoxia and inflammation. While hypoxia post-translationally stabilizes HIF-1alpha protein bacterial stimuli like LPS increase HIF-1alpha by transcriptional processes mediated by NF-kB. Since NF-kB could also be activated under conditions of severe hypoxia / ischemia activation NF-kB is able to enhance the inflammatory upregulation of HIF and HIF target genes. Using siRNA approaches we could also discriminate between HIF and NF-kB dependent hypoxic responses. Survival and migration of cells of the innate and adaptive immune system in a hypoxic microenvironment seems to be HIF-1 dependent whereas ICAM-1 mediated adhesion of leukocytes to endothelial cells depends on the hypoxic induction of NF-kB. Once extravasated from the vasculature the activity of immune cells could be further enhanced by stimulation of HIF-1 by proinflammatory cytokines and locally expressed tissue factors. Cross-talk between hypoxic induction of HIF-1, NF-kB and other signalling pathways activated by inflammation ensures a cell-type specific and stimulus adequate cellular response.