Ischemia-reperfusion injury of the myocardium has long been a subject of intense research. Cardiac preconditioning, an associated phenomenon, has also been critically investigated over the past two decades. Although the biochemistry of ischemia-reperfusion and its association with oxidative metabolism has long been established, recent studies have further revealed a more intricate role of a number of reactive oxygen-nitrogen species in those processes. Emerging evidence suggests that an elaborate network of enzymes (and other biomolecules) dedicated to the generation, utilization, and diminution of reactive oxygen-nitrogen species maintains the redox homeostasis in the myocardium, and any perturbation of its status has distinctive effects. It thus appears that while excessive generation of reactive species leads to cellular injury, their regulated generation may cause transient and reversible modifications of cellular proteins leading the transmission of intracellular signals with specific effects. Taken together, generation of reactive oxygen-nitrogen species in the myocardium plays a nodal role in mediating both ischemic injury and cardioprotection.