Acute pancreatitis generates a complex cascade of immunological events that affect the pathogenesis and the progression of this disease. Several inflammatory mediators seem to play a critical role in the pathogenesis of pancreatitis and the subsequent inflammatory response. In turn, these mediators can influence hemostasis. Coagulation abnormalities occur in acute pancreatitis and are related to its severity. The contribution of blood platelets in the disturbed hemostasis in acute pancreatitis, although extensively studied, remains obscure. This article reviews the local and systemic implications of hemostatic abnormalities during acute pancreatitis. Furthermore, we discuss the prognostic value and the potential therapeutic implications of platelet activation and other hemostatic variables.