There have been considerable advances in the evaluation of suspected acute coronary syndromes (ACS): sophistication of the clinical examination, electrocardiography, risk prediction scores, multiple blood biomarkers, and rapid cardiovascular imaging. Integration of information remains a formidable challenge for the physician in the setting of time-sensitive clinical decision making. In addition to conventional panels of biomarkers, there are novel entities that may be able to signal different stages of the acute event, including plaque disruption, atherothrombosis, ischemic damage, tissue hypoxia, and oxidative stress. The natriuretic peptides are normal myocyte products that reflect myocardial tissue response to neurohormonal and mechanical forces that rapidly change during an ACS event. This article summarizes major advancements in the integrative use of multiple blood biomarkers and cardiovascular imaging in the diagnosis, prognosis, and management of ACS.