Ultrasound (US) can easily penetrate media with excellent spatial precision corresponding to its wavelength. Naturally, US plays a pivotal role in the echolocation abilities of certain mammals such as bats and dolphins. In addition, medical US generated by transducers interact with tissues via delivering ultrasonic energy in the modes of heat generation, exertion of acoustic radiation force (ARF), and acoustic cavitation. Based on the principle of echolocation, various assistive devices for visual impairment people have been developed. High-Intensity Focused Ultrasound (HIFU) are developed for targeted ablation and tissue destruction. Besides thermal ablation, histotripsy with US is designed to damage tissue purely via mechanical effect without thermal coagulation. Low-Intensity Focused Ultrasound (LIFU) has been proven to be an effective stimulation method for neuromodulation. Furthermore, US has been reported to transiently increase permeability of biological membranes, enabling acoustic transfection and blood-brain barrier open. All of these advances in US are changing the clinic. This review mainly introduces the advances in these aspects, focusing on the physical and biological principles, challenges and future direction.