Cells respond to a wide variety of mechanical stimuli, ranging from thermal molecular agitation to potentially destructive cell swelling caused by osmotic pressure gradients. The cell membrane presents a major target of the external mechanical forces that act upon a cell, and mechanosensitive (MS) ion channels play a crucial role in the physiology of mechanotransduction. These detect and transduce external mechanical forces into electrical and/or chemical intracellular signals. Recent work has increased our understanding of their gating mechanism, physiological functions and evolutionary origins. In particular, there has been major progress in research on microbial MS channels. Moreover, cloning and sequencing of MS channels from several species has provided insights into their evolution, their physiological functions in prokaryotes and eukaryotes, and their potential roles in the pathology of disease.