Ultrasound can penetrate deep into tissues and interact with human tissue via thermal and mechanical mechanisms. The ability to focus an ultrasound beam and its energy onto millimeter-size targets was a significant milestone in the development of therapeutic applications of focused ultrasound. Focused ultrasound can be used as a non-invasive thermal ablation technique for tumor treatment and is being developed as an option to standard oncologic therapies. High-intensity focused ultrasound has now been used for clinical treatment of a variety of solid malignant tumors, including those in the pancreas, liver, kidney, bone, prostate, and breast, as well as uterine fibroids and soft-tissue sarcomas. Magnetic resonance imaging and Ultrasound imaging can be combined with high intensity focused ultrasound to provide real-time imaging during ablation. Magnetic resonance guided focused ultrasound represents a novel non-invasive method of treatment that may play an important role as an alternative to open neurosurgical procedures for treatment of a number of brain disorders. This paper briefly reviews the underlying principles of HIFU and presents current applications, outcomes, and complications after treatment. Recent applications of Focused ultrasound for tumor treatment, drug delivery, vessel occlusion, histotripsy, movement disorders, and vascular, oncologic, and psychiatric applications are reviewed, along with clinical challenges and potential future clinical applications of HIFU. HIFU beam can pass through overlying skin and tissues without harm, and focus on a localized area with an upper size limit of approximately 3¨C4 cm in diameter for tumors.?Figure 1 ?shows schematic of a HIFU transducer with focused beam on a tumor. HIFU produces a focused ultrasound beam that passes through the overlying skin and tissues to necrose a localized region (tumor), which may lie deep within the tissues. The affected area at the focal point of the beam leads to lesion coagulative necrosis and is shown in red in?Figure 1. When the tumor is ablated, a very sharp boundary between dead and live cells are created [9]. The boundary width between totally disrupted cells and normal tissue is no more than 50 ¦Ìm [10]. Clinical Applications of HIFU HIFU has been used to treat a variety of solid malignant and benign tumors. HIFU has the advantage of being completely non-invasive, extracorporeal, and non-ionizing modality compared to conventional cancer treatment methods such as chemotherapy, radiotherapy, and open surgery. It is also considered as the only non-invasive technique for both primary solid tumors and metastatic disease treatment. Non tumorous conditions such as prostate hypertrophy have also been treated using HIFU technique. Here we discuss the most frequently used clinical applications of HIFU.