Many of the more than 50 mammalian homologues of the Drosophila transient receptor potential (TRP) channel are likely to play important roles in intracellular Ca²⁺ signalling. The best studied in this respect to date are members of the canonical TRP (TRPC) subfamily which has 7 members (TRPCs1-7). Roles for TRPCs in both store-operated Ca²⁺ entry (SOCE) and Ca²⁺ store-independent (non-capacitatve) Ca²⁺ entry have been proposed. The recent discovery of Orai1, which is likely to constitute the channel responsible for conducting the calcium release-activated current, ICRAC, has overshadowed earlier work on the possible roles of TRPCs in SOCE. However, the characteristics of SOCE in a number of cell types differ from that of the highly Ca²⁺-selective ICRAC and TRPCs or other TRPs may be responsible for conducting the non-selective cation current (Isoc) activated by Ca²⁺ store depletion in such cells. Several members of the TRPC sub-family (all except TRPC6 and TRPC7) have been reported to be activated by Ca²⁺ store depletion. In contrast channels involving TRPC3, TRPC6 and TRPC7 have been shown to be activated by diacylglycerol and thus to generate Ca²⁺ entry which is not dependent on Ca²⁺ store depletion but activated downstream of phospholipase C. The non-selective nature of TRPC channels may allow them to generate Ca²⁺ entry both directly and indirectly, for example elevating cytosolic Na⁺ concentration sufficiently to allow Ca²⁺ entry by reverse mode Na⁺/Ca²⁺ exchange. Supported by the British Heart Foundation and the Wellcome Trust.