Acute atherosclerotic complications, such as myocardial infarction, are often provoked by the rupture of an atherosclerotic plaque and the subsequent thrombotic occlusion of the arterial lumen, which interrupts the blood flow and renders ischemic the downstream peripheral tissue. Several inflammatory mediators (including cytokines, chemokines and matrix metalloproteases) have been shown to orchestrate common pathophysiological mechanisms regulating both plaque vulnerability and myocardial injury. In particular, the selective activation of certain protective intracellular signaling pathways might represent a promising target to reduce the dramatic consequences of an ischemic cardiac event. In the present review we will update evidence on the active role of intracellular kinase cascades (such as mitogen-activated protein kinases [MAPKs], Akt, Janus kinase [JAK]-signal transducer and activator of transcription [STAT]) to reduce the global patient vulnerability for acute myocardial infarction.