Chloride channels are highly selective transport proteins ubiquitously expressed in eukaryotic cells. Biophysical methods allow discrimination between several different types of chloride channels with respect to their gating properties, single-channel conductances and main regulatory mechanisms. The common feature is, however, their high selectivity for chloride ions. Beside the cystic fibrosis transmembrane conductance regulator and ligand-gated channels, five different protein families involved in chloride transport have so far been described in terms of their molecular structure. All of them show distinct structural characteristics and, according to mutation experiments, are believed to be genuine channels.