Recent rapid progress in the field of mechanobiology has been driven by novel emerging tools and methodologies and growing interest from different scientific disciplines. Specific progress has been made toward understanding how cell mechanics is linked to intracellular signaling and the regulation of gene expression in response to a variety of mechanical stimuli. There is a direct link between the mechanoreceptors at the cell surface and intracellular biochemical signaling, which in turn controls downstream effector molecules. Among the mechanoreceptors in the cell membrane, mechanosensitive (MS) ion channels are essential for the ultra-rapid (millisecond) transduction of mechanical stimuli into biologically relevant signals. The three decades of research on mechanosensitive channels resulted in the formulation of two basic principles of mechanosensitive channel gating: force-from-lipids and force-from-filament. In this review, we revisit the biophysical principles that underlie the innate force-sensing ability of mechanosensitive channels as contributors to the force-dependent evolution of life forms.