In the yeast Saccharomyces cerevisiae, Ca2+ signaling mediated by the Ca2+/calmodulin dependent phosphatase, calcineurin, is required for survival during environmental stress. One role of the phosphatase under these conditions is to activate gene expression through its regulation of the Crz1p ("crazy") transcription factor. Calcineurin dephosphorylates Crz1p and causes its rapid translocation from the cytosol to the nucleus. Crz1p then activates the transcription of genes whose products promote cell survival. Recent studies concerning the regulation of Crz1p by calcineurin are discussed in this review and the mechanisms by which calcineurin controls gene expression in yeast and mammalian cells are compared. (C) 2003 Elsevier Inc. All rights reserved.