Oxygen is both an environmental and developmental signal that governs important cellular pathways. Therefore, hypoxia (or low oxygen tensions) is part of both physiological and pathological processes. To deal with hypoxic conditions, cells and organisms have evolved exquisite mechanisms for adaptation and survival. The cellular responses are reliant on controlled transcriptional and post-transcriptional events, where certain genes are positively regulated and others either remain inactive or are actively repressed. It has been known for some time that, during hypoxia, transcription is mainly regulated by the hypoxia inducible factor (HIF). However, recently it has been demonstrated that additional transcription factors are also activated and that non-HIF-dependent processes are involved in the hypoxic stress response. Therefore, gene expression following hypoxia is the result of combined effects on transcription, translation and adjustment mechanisms such as the induction of microRNAs and changes in chromatin.