Background: The ubiquitin-proteasome system (UPS) is one of the major non-lysosomal pathways for intracellular degradation of proteins and plays a significant role in regulating many cellular processes. It was reported recently that UPS regulates importantly many cardiac pathological conditions also. Objective: UPS dysfunction was found to be associated with myocardial ischemia-reperfusion injury9IRI). However, the role of ubiquitin-proteasome system in myocardial protection remained controversial. Content: The studies about role of the UPS in myocardial ischemia, the effect of proteasome inhibitors in myocardial protection and the effects of ischemic preconditioning and volatile anaesthetics preconditioning on UPS were reviewed. Trend: It's obvious that further understanding of UPS myocardial protection on IRI needs additional investigation.