Coronary heart disease is the leading cause of mortality worldwide, affecting millions of men and women every year. Elucidation of key signaling factors and their pathways are critical for understanding and developing novel therapeutic targets for protection of the myocardium from ischemia. EGR-1, an immediate early gene and a zinc finger transcription factor plays critical role in various cardiovascular patho-biological processes. This article reviews the growing evidence implicating EGR-1 pathway in myocardial ischemia/reperfusion, cardiac hypertrophy and other cardiovascular complications like atherosclerosis.