The ClC proteins are members of a large family of chloride transport proteins, which are involved in a variety of physiological processes. All family members share a conserved molecular architecture consisting of a complex transmembrane transport domain and a soluble regulatory domain. To date, representative structures for the two parts are available, the transmembrane domain from the structure of a bacterial homologue, the soluble domain from a eukaryotic family member. Despite the strong conservation of the structural framework, the family members show an unusually broad variety of functional behaviors, as some members work as gated chloride channels and others as secondary chloride transporters. The conservation in the structure and the functional resemblance in gating and transport mechanism suggest a strong mechanistic relationship between seemingly contradictory transport modes.