The treatment of cancer continues to rest largely on three major modalities: surgery, radiotherapy and systemic therapies, including chemotherapy. To these we can add a number of other approaches: immunotherapy, targeted therapy and gene therapy. The use of ionizing radiation to treat cancer started soon after the discovery of radium by M.S. Curie and P. Curie in 1898 (see Milestones in Cancer Therapy and Imaging). The first histologically documented cancer cures using radiation were in St. Petersburg in 1903 by S.W. Goldberg and Efim Semenovich London. These cases were reported in Dermatologische Zeitschrift [I.1] and described patients with basal cell carcinoma of the face. However, unlike the first documented histological cures by X rays (also for basal cell carcinoma of the face in 1899 in Stockholm) [I.2], no photographs are available of the patients treated in St. Petersburg before and after treatment. More than a century after the discovery of radium, radiation medicine interventions continue to play a major role in the various stages of the continuum of cancer care: prevention, early detection and screening, diagnosis, treatment and palliative care. In this context, radiotherapy is an important contribution to the cure of many patients and to effective palliation in many others. Radiotherapy is currently an essential component in the management of cancer patients, either alone or in combination with surgery or chemotherapy, both for cure and for palliation. Of those cancer patients who are cured, it is estimated that 49% are cured by surgery, about 40% by radiotherapy alone or combined with other modalities, and 11% by chemotherapy alone or combined [I.3]. The mechanism by which radiotherapy is effective in the treatment of cancer is described in more detail in Chapter 6. Clearly, ionizing radiation in sufficient doses has a cell killing effect, but it is not specific enough to differentiate between cancerous and normal cells. Strategies had to be found to improve the therapeutic index, either by physically improving target conformity or by increasing the radiation sensitivity of the cancer cells relative to the normal cells. The main objective guiding the historical development of radiotherapy has always been the delivery of a curative radiation dose to the malignant tumour, while minimizing the dose received by healthy tissues and organs, thus optimizing the therapeutic index. This has been the ultimate goal of radiotherapy strategies 4 such as the use of hyperthermia, hyperbaric oxygen, high linear energy transfer (LET) radiation, radiosensitizers, concomitant chemoradiotherapy, manipulation of fractionation schemes and modulation of the radiation fluence. In recent years, research into the molecular basis of radiation response in tumours and in normal tissues under various physiological and pathophysiological situations has continued to