The EF-hand homolog proteins bind calcium (Ca2+) with dissociation constants in the micromolar range and are modulated by stimulus-induced increases in cytosolic free Ca2+. We have grouped over 160 different EF-hand homolog proteins into ten subfamilies and ten unique categories. Except for troponin-C, all subfamilies and unique EF-hand homologs represented in vertebrates can be found in the CNS. In this review, structural and functional characteristics of these proteins are discussed, with special emphasis on the multifunctional regulatory protein, calmodulin. The possible function of bending within the central helix of calmodulin is considered and is illustrated with a model calmodulin--target complex.