The nuclear factor of activated T cells (NFAT) proteins are a family of transcription factors whose activation is controlled by calcineurin, a Ca(2+)-dependent phosphatase. Originally identified in T cells as inducers of cytokine gene expression, NFAT proteins play varied roles in cells outside of the immune system. This review addresses the recent data implicating NFAT in the control of gene expression influencing the development and adaptation of numerous mammalian cell types.