The behavior of lymphocytes in the immune system depends on encounters with antigens. These bind to immunoreceptors on the surface of T-cells and B-cells, activating a variety of signal transduction pathways that control cell survival, proliferation, differentiation, and effector functions. Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Biology includes contributions covering the structures of the T-cell and B-cell immunoreceptors, the numerous kinases and adaptors that associate with their intracellular tails, and the downstream signaling pathways that lead to transcription of interleukins and other outputs. Other contributions examine the roles of other receptors, co-stimulatory signals, and innate immune responses in regulation of immunoreceptor signaling. The spatial organization of the immunological synapses connecting lymphocytes and antigen-presenting cells is also discussed, along with the role of the cytoskeleton in immunoreceptor function. Computational models of the signaling processes complete the volume, making it essential reading for systems biologists as well as all immunologists and cell biologists interested in understanding how lymphocytes function.