The cellular response to an extracellular signal starts with the induction of a signaling cascade that transmits the signal through the cytoplasm to the nucleus, resulting in the activation of transcription factors that activate specific target genes. The signaling cascade involves a series of biochemical modifications that include phosphorylation events on tyrosine residues due to the activation of specific protein kinases. Recently, evidence accumulated that reactive oxygen species, including hydrogen peroxide, superoxide, and the hydroxyl radical, are important chemical mediators that regulate the transduction of signals from the membrane to the nucleus by modulating the protein activity by oxidation and reduction. In this report, the redox regulation of signaling involving protein tyrosine kinase activity, in particular in T- and B-lymphocyte signaling, is reviewed.