Nuclear factor of activated T cell c (NFATc) transcription factors appeared in evolution with the emergence of lymphocytes in jawed fish. They have decisive roles in the development of the immune system and adaptive immune responses. Following immunoreceptor stimulation, NFAT factors control the expression of a large set of genes and thereby the fate of peripheral lymphocytes. NFATc1 and NFATc2 are the most prominent NFAT factors in peripheral T cells; they overlap in their function but differ remarkably in the mode of expression. NFATc2 is constitutively synthesized in T cells, whereas the expression of NFATc1/alphaA, the most prominent of six NFATc1 isoforms in peripheral T cells, is strongly induced following T-cell receptor and co-receptor stimulation and maintained by positive autoregulation. Findings concerning NFATc1 autoregulation in peripheral T lymphocytes and other cells suggest that positive autoregulation of NFATc1 is a crucial step in cell-fate determination.