Recognition of the antigen/MHC complex by the T cell receptor (TCR)-CD3 complex in T cells triggers early activation events such as tyrosine phosphorylation, phosphatidylinositol turnover, intracellular Ca2+ mobilization or activation of protein kinases, and finally exhibits effector functions such as lymphokine secretion by helper T cells or cytotoxicity by killer T cells as late activation events. Several key molecules have been shown to engage in these signaling cascades. In addition to the TCR-CD3 molecules, other surface molecules such as CD28 or LFA-1 contribute to the regulation of T cell activation as a co-stimulator. Growing knowledge about the downstream of antigen recognition is promoting the attempt to modulate the signal transduction by specific drugs, mAbs, altered peptides or cytokines. Further investigations on the molecular mechanism of T cell activation will provide clinical successes to control immune responses.