In B cells, changes in intracellular concentration of Ca 2+ drive signal transduction to initiate changes in gene expression and various cellular events, including apoptosis and differentiation. B cell receptor engagement causes a transient Ca 2+ flux from the endoplasmic reticulum Ca 2+ store, followed by a continuous increase in intracellular Ca 2+ concentration, mainly resulting from store-operated Ca 2+ entry (SOCE). The recent identification of stromal interaction molecule (STIM) and Orai as essential components for SOCE has allowed researchers to probe further the role of Ca 2+ signals in B cell biology. Here, we summarize the B cell signaling pathways that lead to SOCE, the role of Ca 2+ signals in B cell regulatory function, and how a breakdown in the balance of Ca 2+ signals is associated with immune-related disease.