Current technologies make it possible to study thousands of genes simultaneously in the same biological sample - an approach termed gene expression profiling. Several techniques, including (i) differential display, (ii) serial analysis of gene expression (SAGE), (iii) subtractive hybridization and (iv) gene microarrays (Gene Chips), have been developed. Recently, gene profiling was applied in studying the mechanisms of ischemic injury and ischemic preconditioning. In the case of reversible ischemia caused by one or several brief transient episodes of complete coronary occlusion (as with ischemic preconditioning), or with a more prolonged but partial coronary ligation, many up-regulated genes were related to the "cell survival program". Protective genes included mitogen-activated protein kinase-activated protein kinase 3 (MAPKAPK 3), heat shock proteins 70, 27, 22, B-crystalline, vascular endothelial growth factor, inducible nitric oxide synthase and plasminogen activator inhibitors 1 and 2. With permanent coronary occlusion lasting from 24 h to several weeks, and resulting in a true myocardial infarction (MI), the list of up-regulated genes included those related to remodeling (e.g., collagens I and III, fibronectin, laminin) and apoptosis (Bax), while many down-regulated genes were related to major energy-generating pathways in the heart, namely, fatty acid metabolism. Gene expression profiling experiments have resulted in the discovery of two different genetic programs in the heart, namely, a protective program activated upon brief episodes of transient ischemia and an injury-related one activated in response to irreversible ischemic injury. Searching for factors turning on protective genes, and turning down injury-related ones, is a justifiable approach in developing new therapeutic strategies aimed to fight ischemic heart disease.