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Inflammation plays an integral role in atherogenesis and the pathogenesis of coronary artery disease (CAD). The question remains as to whether targeted inhibition of specific pathways of inflammation will have any clinical benefits in CAD. In this article, we will review p38 mitogen-activated protein kinase, one of the key sensors of cellular stress that plays an important role in the inflammatory cascade. In addition, we will review losmapimod, a reversible competitive inhibitor of the α and β isoforms of p38 mitogen-activated protein kinase, and its efficacy when added to standard of care in patients hospitalized with myocardial infarction. In the phase III trial, LATITUDE-TIMI 60, the investigators found that treating patients hospitalized with acute myocardial infarction with losmapimod did not reduce the risk of major adverse cardiovascular events. Lastly, we will briefly review trials recently completed and currently underway, investigating other anti-inflammatory medications such as canakinumab, methotrexate, varespladib, darapladib, and colchicine, and their role in CAD.