Many ion channels have been described as mechanosensitive according to various criteria. Most broadly defined, an ion channel is said mechanosensitive if its activity is controlled by application of a physical force. The last decade has witnessed a revolution in mechanosensory physiology at the molecular, cellular and system levels, both in health and diseases. Since the discovery of the PIEZO proteins as prototypical mechanosensitive channel, many proteins have been proposed to transduce mechanosensory information in mammals. However, few of these newly identified candidates have all the attributes of bona-fide, pore-forming mechanosensitive ion channels. In this Perspective, we will cover and discuss new data that have advanced our understanding of mechanosensation at the molecular level.