During acute myocardial infarction (MI), the cumulative loss of functioning cardiomyocytes (CM) progresses as an imbrication of necrosis, apoptosis, and autophagy. Coronary artery occlusion and subsequent hypoxia causes some CMs to undergo necrosis with most cellular damage occurring near the area of occlusion. The inflammation that ensues plays a critical role in the reparative process and occurs in parallel as CMs struggle to survive. The release of inflammatory pro-apoptotic cytokines compounded with activation of apoptosis results in the programmed death of ischemic CMs. Concurrently, the level of autophagic flux in border zone CMs will determine whether or not these CMs are able to survive hypoxic cellular conditions. The interplay of these processes and the balance that occurs in the peri-infarct area plays a pivotal role in preserving the functional capacity of CMs, specifically through the upregulation of autophagy and downregulation of apoptosis and inflammation. A detailed understanding of these signaling pathways in acute MI is necessary to develop novel therapeutics to promote CM survival and diminish CM death following MI. This review discusses the cellular processes of necrosis, apoptosis, autophagy, and inflammation that occur during acute MI. Also, the common signaling mediators that each process employs and their relationship to each other are discussed to provide a better understanding of these synergistic effects during MI.