Cl(-) channels are widely found anion pores that are regulated by a variety of signals and that play various roles. On the basis of molecular biologic findings, ligand-gated Cl(-) channels in synapses, cystic fibrosis transmembrane conductors (CFTRs) and ClC channel types have been established, followed by bestrophin and possibly by tweety, which encode Ca(2+)-activated Cl(-) channels. The ClC family has been shown to possess a variety of functions, including stabilization of membrane potential, excitation, cell-volume regulation, fluid transport, protein degradation in endosomal vesicles and possibly cell growth. The molecular structure of Cl(-) channel types varies from 1 to 12 transmembrane segments. By means of computer-based prediction, functional Cl(-) channels have been synthesized artificially, revealing that many possible ion pores are hidden in channel, transporter or unidentified hydrophobic membrane proteins. Thus, novel Cl(-)-conducting pores may be occasionally discovered, and evidence from molecular biologic studies will clarify their physiologic and pathophysiologic roles.