Ca 2+ homeostasis controls a diversity of cellular processes including proliferation and apoptosis. A very important aspect of Ca 2+ signaling is how different Ca 2+ signals are translated into specific cell functions. In T cells, Ca 2+ signals are induced following the recognition of antigen by the T cell receptor and depend mainly on Ca 2+ influx through store-operated CRAC channels, which are mediated by ORAI proteins following their activation by STIM proteins. The complete absence of Ca 2+ influx caused by mutations in Stim1 and Orai1 leads to severe immunodeficiency. Here we summarize how Ca 2+ signals are tuned to regulate important T cell functions as proliferation, apoptosis and tolerance, the latter one being a special state of immune cells in which they can no longer respond properly to an otherwise activating stimulus. Perturbations of Ca 2+ signaling may be linked to immune suppressive diseases and autoimmune diseases.