T-cell receptor (TCR) engagement by antigen results in proliferation, differentiation and cytokine secretion. In the CD8+ T-cell subset, TCR triggering also induces granule exocytosis, the directional release of contents of lysosome-like granules toward the target cell presenting the antigen. This process is responsible for immediate death of target cells. The intracellular events required for granule exocytosis are distinct from those of proliferation and cytokine secretion, as the former do not require de novo protein synthesis. Consequently, the key TCR signaling events required for granule exocytosis may be distinct. In this article, we review present knowledge of regulation of granule exocytosis by molecules of the TCR signaling cascade.