Image-guided frameless fractionated stereotactic radiotherapy can be performed with millimetric accuracy using the CyberKnife (Accuray Inc. Sunnyvale, USA) equipped with an integrated tracking system for intra- and extracranial lesions. Highly conformal hypofractionated irradiation has been used to treat lesions with curative or palliative intent. It is advantageous for radioresistant tumors, re-irradiating lesions, boosting small volumes and treating tumors that move with respiration. It also limits travel costs and improves the quality of life. Over 60,000 patients have been treated worldwide using CyberKnife including 600 patients in the three French cancer centres of Nice, Nancy and Lille. These expert Cyberknife centres follow quality assurance programs and work together with the "Haute Autorité de santé" and the French National Cancer Institute (INCa) to promote clinical developments. The CyberKnife has been used to treat intracranial lesions including (but not limited to) meningiomas, acoustic schwannomas, brain oligometastases, as well as skull base tumors like chordomas, or para- or intraspinal tumors, and extracranial tumors such as lung cancers. Currently, extracranial stereotactic radiotherapy is particularly attractive for tumors moving with respiration and is being evaluated in liver, prostate and re-irradiation including head and neck tumors.