In radiobiology, the hypoxic cells have been shown to be more resistant to irradiation as compared to cells irradiated in conditions of normal oxygenation. Moreover, most solid tumors contain foci of clonogenic cells able to cause the failure of radiotherapy and the development of more aggressive phenotypes. To-date, numerous techniques allow the detection and quantitation of tumor hypoxia in many tumors and to correlate it with the clinical course. The impact of tumor hypoxia is evident from a careful analysis of data of several trials where the solution of the problem was attempted. In recent years, new functional imaging procedures, assays of molecular biology and new drugs that act directly on hypoxic cells, have been introduced. In the near future, this might lead to the control of this negative clinical impact of hypoxia.