Cyclic nucleotides are second messengers exerting their cellular effects mainly through protein phosphorylation. A new member of this family, cyclic ADP-ribose, is involved, instead, in mediating mobilization of Ca+2 from internal stores. The structure of this nucleotide has now been determined by X-ray crystallography and accumulating evidence indicates it may be an endogenous modulator of the Ca+2 induced Ca+2 release mechanism. This article summarizes the current knowledge of the structure, the mechanism of action and the metabolic enzymes of this novel nucleotide. With this new addition, the signalling functions of the cyclic nucleotide family are now extended from protein phosphorylation to Ca+2 signalling.