Protein phosphorylation is one of the major key regulatory mechanisms by which extracellular signals are transmitted into cells such as platelets. Virtually all types of extracellular signals that activate platelets produce most of their diverse physiological effects by regulating phosphorylation of specific proteins. Although proteins may be covalently modified in many other ways, including acylation (acetylation, myristylation, isoprenylation), carboxymethylation, ubiquitylation, tyrosine sulfation, and glycosylation, none of these mechanisms are nearly as widespread as protein phosphorylation. Protein phosphorylation regulates the structures and functions of cellular proteins in a wide spectrum of platelet processes, including platelet aggregation, secretion, spreading, and clot retraction. Thus, protein phosphorylation is by far the most prominent mechanism through which platelets regulate their functional responses.