The mitochondrion is a vital component in cellular energy metabolism and intracellular signaling processes and they are involved in a myriad of complex signaling cascades regulating cell survival vs death.Mitochondrial dysfunction and the resulting oxidative stress are central in the process of I/R injury.Alleviating the mitochondrial dysfunction will contribute to mitigating the severity or progression of the myocardial injury.Recently, advances in mitochondrial biology have led to selective targeting of drugs designed to modulate or manipulate mitochondrial function.This review will provide an overview of the potential role for targeting mitochondria with potential drugs that lead to protect against cell injury.