Lipid mediators generated from arachidonic acid through the action of 5-lipoxygenase have been known for over two decades and are implicated in a wide variety of inflammatory disorders. G-protein-coupled receptors mediate the effects of different leukotrienes in distinct cell types. Novel cellular and molecular targets were recently discovered for these mediators, with important consequences for the function of both adaptive and innate immune systems. These studies have outlined crucial new roles for leukotrienes in the recruitment of T lymphocytes and in the development of atherosclerotic lesions, suggesting novel mechanisms for their actions. Through the development of appropriate animal models, leukotrienes are becoming renewed targets for treatment of many inflammatory diseases including atherosclerosis.