The discovery that previously unidentified allosteric properties of several proteins, such as fibrinogen and myoglobin, can be triggered by anions binding, has suggested the possibility to design a new "active" role of chloride in the modulation of a broad range of biological systems. The molecular bases of the anions binding to proteins depends by their charge density in turn regulating the ability to bind water molecules and interact with basic groups on proteins. This review reports the role of the physiologically relevant chloride, and of other anions, in the regulation of several proteins, with special attention to the coagulation cascade. Moreover, possible mechanisms of modification of plasma, intra- or extracellular chloride concentration are listed.