T lymphocytes utilize a variety of surface receptors to transmit environmental signals across the plasma membrane and initiate biochemical events leading to responses such as proliferation, anergy, cytokine secretion, and death. The T cell receptor complex, CD28, IL-2 receptor, and CD95 each couple to distinct sets of cytoplasmic signaling events to modulate the biological responses of T cells. Deficiency or defective function of proteins involved in signaling through these receptors are associated with murine and human disease.