Various studies have investigated the effects of glycogen synthase kinase (GSK) 3beta which plays a fundamental role in the regulation of the activity of nuclear factor kappaB, in the inflammatory process. In particular, it has been demonstrated that the GSK-3beta inhibition, using genetically modified cells and chemically different pharmacological inhibitors, affects the regulation of various inflammatory mediators in vitro and invivo. Moreover, recently, Insulin, an endogenous inhibitor of GSK-3, has been clinically used in the therapy for septic shock. The beneficial anti-inflammatory effects of insulin in preclinical and clinical studies could possibly be due, at least in part, to the inhibition of GSK-3 and not directly correlated to the regulation of blood glucose. In this review, we discuss briefly the present understanding of (GSK) 3beta-mediated biology and the current therapies in clinical use, and focus on some of the new therapeutic approaches with pharmacological inhibitors for the treatment of several inflammatory diseases like ischemia-reperfusion injury and trauma.