Myocardial apoptosis primarily triggered during reperfusion has been associated with cardiac dysfunction and extension of infarction. Although potential signaling pathways involved in triggering apoptosis remain to be clearly defined, an increasing number of experiments have implicated the generation of reactive oxygen species (ROS). Increased levels of ROS have been shown to cause inflammatory and endothelial cell-cell interactions and calcium overload, resulting in enhanced release of pro-apoptotic genes from mitochondria. ROS also activate mitogen-activated protein kinases, stimulate nuclear factor-kappaB and promote synthesis of tumour necrosis factor-alpha. Attenuation of apoptosis by antioxidants has opened a new therapeutic window in the treatment of ischemia/reperfusion injury.