The complex cellular interactions that govern the mammalian immune response are now known to include specific receptor/ligand interactions, recruitment of intracellular signaling molecules, activation of both kinases and phosphatases, and redistribution of macromolecular complexes into specific subcellular membrane locations that, in aggregate, result in transcriptional activation. While the TCR-CD3 signal is critical for activation of the resting T cell, it alone is not sufficient to initiate transcriptional activation or generate an effective immune response. A number of other coreceptor molecules, including CD4, CD8, and CD28, have now been characterized that also play important roles in initiating or amplifying the activation of the T cell. A 40 kDa member of the immunoglobulin superfamily, the CD7 molecule, has also been shown to have costimulatory activity and to induce tyrosine and lipid kinase activities. Here we will review the signaling pathways initiated by TCR, CD28, and CD7, as well as the functional consequences of signal transduction through these receptors.