Antibodies produced by B cells play an essential role in protecting against disease-causing pathogens. B cells detect the presence of pathogens via B-cell antigen receptors (BCRs), which consist of a transmembrane form of an antibody that is associated with a signaling subunit. Signaling by BCRs not only initiates antibody production but also regulates B-cell development, B-cell survival and the elimination of B cells that recognize components of one's own body. Identifying the intracellular signals generated by BCRs and determining how these signals specify such diverse responses is the key to understanding how the immune system functions normally and how defects in BCR signaling can lead to either immunodeficiency diseases or autoimmune diseases.