Mechanisms governing platelet-mediated tissue repair. Platelets are cellular mediators that orchestrate clinically relevant but still poorly understood mechanisms of tissue repair. They release cytokines, chemokines, and growth factors such as SDF-1 and HGF that control recruitment, proliferation, and activation of fibroblasts, neutrophils, monocytes, SMCs, MSCs, and other cell types critically involved in wound healing. Platelets also regulate angiogenesis in damaged tissue, which is another important mechanism for recovery of tissue function. Recruitment of progenitor cells, including MSCs, SMCs, endothelial progenitors, and CD34-positive progenitors, is influenced by platelets as well, promoting wound repair at least partially due to paracrine mechanisms. Moreover, platelets are capable of modulating the balance between apoptosis and cell survival, which determines the pathophysiology of damaged tissues. They can release proapoptotic (Fas-L, CD40L, TRAIL, TWEAK, and LIGHT) as well as antiapoptotic (HGF, SDF-1, serotonin, adenosine diphosphate, and sphingosine-1-phosphate) mediators. Moreover, microparticles derived from platelets can regulate apoptosis in endothelial cells and SMCs as well as provide survival signals to monocytic, endothelial, and neural stem cells. Granzyme B is a mediator of platelet-induced apoptosis in spleen and lung. HMGB1, a danger signal that is exported to the cell surface by platelets upon activation, regulates apoptosis as well as autophagy in tumor cells depending on its redox status. Therefore, platelets control complex mechanisms of tissue repair. ADP, adenosine diphosphate; CD62P, P-selectin; CM, cardiomyocyte; EC, endothelial cell; MØ, macrophage; MP, microparticle; NSC, neural stem cell; pAkt, phosphorylated Akt; PC, progenitor cell; ROS, reactive oxygen species; Ser, serotonin; SP-1, sphingosine-1-phosphate; TC, tumor cell.