Like many nucleated mammalian cells, the life and death of the anucleate platelet is regulated by Bcl-2 family proteins. Platelets depend on Bcl-x(L) for survival. Bcl-x(L) maintains platelet viability by restraining the killer protein Bak. When Bak is unleashed, it triggers classical intrinsic apoptosis by causing mitochondrial damage. The latter leads to caspase activation and phosphatidylserine (PS) exposure. Platelet apoptosis can be blocked by caspase inhibitors, or by genetic deletion of Bak and its close relative Bax. Perturbations in the platelet apoptosis program lead to changes in platelet life span in vivo. Here, we describe methods to determine platelet life span, enumerate young platelets, and measure hallmarks of platelet apoptosis, such as PS exposure, caspase activation, and mitochondrial dysfunction.