Over the past 10-15 years, developments in gene expression profiling have opened new arenas for the discovery of important factors in the pathogenesis of numerous disease processes, including coronary artery disease. Messenger RNA and microRNA are differentially expressed in patients with coronary plaques, acute plaque rupture, and response to well-established treatments for acute coronary syndromes. In this review, we will explore recent developments in messenger RNA and microRNA technology at each stage of a patient's progression through the natural history of cardiovascular disease, including evaluation of risk factors, prediction and detection of coronary artery disease and acute coronary syndromes, and finally, response to treatments for coronary artery disease and its sequelae including congestive heart failure.