Maintaining a precise calcium (Ca2+) balance is vital for cellular survival. The most prominent pathway to shuttle Ca2+ into cells is the Ca2+ release activated Ca2+ (CRAC) channel. Orai proteins are indispensable players in this central mechanism of Ca2+ entry. This short review traces the latest articles published in the field of CRAC channel signalling with a focus on the structure of the pore-forming Orai proteins, the propagation of the binding signal from STIM1 through the channel to the central pore and their role in human health and disease.