Several candidate mechanosensitive channels have been identified in single and multicellular organisms. In prokaryotes, the well-characterized channels are gated by force that conveys lateral tension in the membrane. These channels, while sharing certain transmembrane motifs, are molecularly distinct from the two families of putative mechanosensory channels of multicellular organisms, the transient receptor potential (TRP) and the degenerin/epithelial sodium channel (DEG/ENaC) family of genes. DEG/ENaC channels have been best characterized in certain fine-touch sensory cells of nematodes, but have also been found to be present in cutaneous sensors of flies and free nerve endings as well as specialized nerve endings of vertebrates. Several TRP channels have been associated with mechanosensation in nematodes and flies and have also been implicated in hair cell mechanotransduction. In nematodes, flies, and vertebrates numerous distinct intra- and extracellular proteins play a seemingly variable role in anchoring the putative channel to improve performance. It is proposed that single ancestral unicellular channels have been modified in the course of evolution to allow different functions in various sensations, including mechanosensation in variable cells and organs.