Hypoxia is an important feature of the microenvironment of a wide range of solid tumours. Its critical role in radio- and chemoresistance and its significance as an adverse prognostic factor have been well established over the last decades. On a cellular level, hypoxia evokes a complex molecular response with a central role for the HIF-1 pathway. The cellular processes under control of HIF-1 contain important prognostic information and comprise potential candidates for directing hypoxia-modifying therapies. This review will provide an overview of the current knowledge on the molecular aspects of tumour hypoxia and the link to clinical practice.