Blood clot contraction (retraction) is the process of clot shrinkage occurring both in vitro and in vivo, which is driven by the contractile activity of activated platelets attached to the fibrin network. The molecular mechanisms behind blood clot contraction involve mainly the force-generating actomyosin machinery within the platelets and mechanotransduction, that is, transmission of the intracellular traction force to the extracellular fibrin. Platelets adhere to fibrin through the αIIbβ3 integrin receptors, and the mechanical forces generated within platelets are transmitted to the fibrin fibers, followed by the distribution of the forces throughout the fibrin network and the compaction of the clot. Contraction is accompanied by redistribution of the fibrin-platelet meshwork to the clot periphery and accumulation and compressive deformation of erythrocytes to polyhedrocytes in the core. Blood clot contraction has significant pathophysiological and clinical relevance, as it is crucial both for hemostasis and thrombosis. In hemostasis, blood clot contraction helps to form an impermeable seal and bring the wound edges closer together. In thromboses of various etiologies and locations, clot contraction affects thrombus obstructiveness, lytic resistance, and predisposition to embolization. Understanding blood clot contraction is important for designing new treatment modalities to prevent or treat various hemostatic and thrombotic disorders.