Background　Glycogen synthase kinase 3β（GSK-3β） is a multifunctional serine threonine kinase that plays important roles in cell metabolism， growth， differentiation and apoptosis. GSK-3β is a vital component of several signal transduction pathways with the ability to phosphorylate the substrates.　Objective　This review will focus on issues regarding the roles of GSK-3β in myocardial ischemia/reperfusion injury（I/RI） and its protection.　Content　The actived GSK-3β can amplify the inflammatory response， induce the irreversibly high level opening of the mitochondrial permeability transition pore and activate the apoptotic pathways in turns that aggravates myocardial I/RI， whereas depressing activation of GSK-3β can significantly improve the tolerance of heart to the I/RI. In addition， the abnormal status of GSK-3β and the related signal transduction pathways are the critical reasons for the impaired cardioprotection of many protective interventions in the comorbidities.　Trend　The recovery of sensibility of GSK-3β and the related signal transduction pathways may help to address the difficulty of translating the outcomes of the basic researches on myocardial I/RI to the clinic.