As targets for the immunosuppressive drugs cyclosporin A and FK506,transcription factors of the NFAT (nuclear factor of activated T cells) familyhave been the focus of much attention. NFAT proteins, which are expressed inmost immune-system cells, play a pivotal role in the transcription of cytokinegenes and other genes critical for the immune response. The activity of NFATproteins is tightly regulated by the calcium/calmodulin-dependent phosphatasecalcineurin, a primary target for inhibition by cyclosporin A and FK506.Calcineurin controls the translocation of NFAT proteins from the cytoplasm tothe nucleus of activated cells by interacting with an N-terminal regulatorydomain conserved in the NFAT family. The DNA-binding domains of NFAT proteinsresemble those of Rel-family proteins, and Rel and NFAT proteins show someoverlap in their ability to bind to certain regulatory elements in cytokinegenes. NFAT is also notable for its ability to bind cooperatively withtranscription factors of the AP-1 (Fos/Jun) family to composite NFAT:AP-1sites, found in the regulatory regions of many genes that are induciblytranscribed by immune-system cells. This review discusses recent data on thediversity of the NFAT family of transcription factors, the regulation of NFATproteins within cells, and the cooperation of NFAT proteins with othertranscription factors to regulate the expression of inducible genes.