Recent studies have reported that the ischemia/reperfusion (I/R) myocardium may act as an immune system where an exaggerated inflammatory reaction initiates. With activation of the immune system, damage-associated molecular patterns migrate and adhere into the I/R region and, consequently, induce myocardial injury. Emerging data have indicated that the adaptor proteins Crk are thought to play essential roles in signaling during apoptosis and cell adhesion and migration. Accumulated data highlight that Crk proteins are potential immunotherapeutic targets in immune diseases. However, very few studies have determined the roles of Crk on myocardial I/R injury. This mini review will focus on the emerging roles of Crk adaptors during myocardial I/R injury.