Store-operated Ca2+ entry (SOCE) mediates much of the Ca2+ entry evoked by receptors that stimulate phospholipase C. However, for 20 years, the plasma membrane Ca2+ channel and the signal linking its activation to loss of Ca2+ from the endoplasmic reticulum (ER) have eluded detection. But the search might now be over. Two proteins, STIM1 (the ER Ca2+ sensor) and Orai1 (the Ca2+ channel), have recently been identified as the missing links in SOCE.