Acute pancreatitis (AP) is a human disease characterised by inflammation and necrosis of the pancreas. Intracellular activation of enzymes, the hallmark of AP, has been shown to be the result of sustained elevations in [Ca2+]i 1,2. Pathophysiological Ca2+ signals that precede AP, deplete the endoplasmic reticulum (ER) Ca2+ stores. ER store depletion is detected by the ER Ca2+ sensor, stromal interaction molecule 1 (STIM1), which activates Ca2+-release activated Ca2+ (CRAC) channels located in the plasma membrane 3. CRAC channels, a type of store-operated Ca2+ channels (SOCC), open in response to Ca2+ store depletion to refill the ER in non-excitable cells 3. However, during pathological stimulation additional Ca2+ entering the cell will only serve to further increase already elevated [Ca2+]i concentrations. CRAC channels are an ideal target in order to reduce Ca2+overload. C57BL/6 mice were killed humanely in accordance with the UK Schedule 1 of the Animals (Scientific Procedures) Act, 1986. [Ca2+]i measurements were made using cells loaded with the Ca2+-sensitive dye, Fura-2.When cells are treated with compounds that inhibit CRAC channels, such as GSK-7975A4, Ca2+ influx is markedly reduced compared with control cells and so is the necrotic cell damage associated with AP. 2-APB has traditionally been viewed as a blocker of SOCC, but has deleterious effects in pancreatic acinar cells by releasing Ca2+ from ER stores. Recently more potent analogues of 2-APB have been developed and when applied to pancreatic acinar cells can reduce Ca2+ influx, in a dose dependent manner. Calmodulin (CaM) and Ca2+-like peptides (CALPs) have been shown to be protective against ethanol-invoked increases in [Ca2+]i 5. CRAC channels have a known CaM binding domain and contribute to [Ca2+]i overload; our studies using agonists, such as CALPs, and antagonists of CaM indicate that pharmacologically targeting CaM affects Ca2+ entry. Data collected using 2-APB analogues supports the data obtained using GSK-7975A4, inhibiting CRAC channels reduces Ca2+ overload in cells. Peptides, like CALP-35, also seem to have promise in reducing Ca2+ overload. A combination of CRAC channel blockers and CaM modulation may be a more efficient method of reducing Ca2+ overload and act as a potential AP therapy.