Platelet activation induces a rapid redistribution of phospholipid asymmetric orientation within the plasma membrane due to simultaneous calcium-dependent inhibition of flippase activity and activation of scramblase. As a result, the anionic phospholipid phosphatidylserine (PS) becomes exposed on the outer leaflet of the platelet plasma membrane, providing a critical platform for the activation of thrombin generation. The binding of blood-clotting enzyme complexes to this procoagulant membrane surface dramatically increases the conversion of zymogens to active serine proteases, thereby driving a thrombin burst, leading to fibrin clot formation and further platelet activation. The energy-independent and calcium-dependent platelet scramblase TMEM16F, which governs the bidirectional exchange of phospholipids between the two leaflets of the bilayer, is essential for PS exposure during platelet activation. The last decade brought tremendous progress in the understanding of the anionic phospholipid scrambling process, the characterization of procoagulant platelets, and the identification of TMEM16F loss-of-function mutations responsible for Scott syndrome, a bleeding disorder caused by impaired platelet procoagulant activity.