The idea to ablate brain tissue with high-intensity focused ultrasound (HIFU) in a highly precise and localized manner is relatively old. For HIFU tissue ablation, ultrasound (US) waves are concentrated to a focal point. Due to US absorption, the focal area will be heated and consequently thermally destroyed. The spatial accuracy of the non-invasive procedure and the sharp delineation of the induced tissue lesions have led to the term 'focused ultrasound surgery' (FUS). The major obstacle for HIFU ablation in the brain is the skull bone, which absorbs most of the US energy and disturbs the focused US field. The development of large-sized phased array US transducers and adaptive focusing techniques based on computed tomography images have allowed these difficulties to be overcome. With the combination of FUS and MR-imaging and MR-thermometry (MR-guided Focused Ultrasound Surgery, MRgFUS), real-time therapy guidance and control has been established. The safety, feasibility and effectiveness of transcranial MRgFUS were investigated in four initial clinical studies including 4 to 15 patients each. In the first study, which dealt with the treatment of inoperable recurrent glioblastoma, MR was used to monitor localized tissue heating, but no tissue ablation was possible due to technical restrictions of the treatment setup. With improved equipment, the precise induction of thermal lesions in the target area was achieved in studies on neuropathic pain and essential tremor. An instantaneous and persistent significant improvement of disease symptoms was observed in most patients. However, there were serious adverse effects in two cases, where intracranial hemorrhages appeared due to the induction of cavitation. Based on these encouraging clinical results, more extensive clinical studies have been initiated. Transcranial MRgFUS is a fast-growing field of neurological research with high clinical potential.