Leukotrienes (LTs) are inflammatory mediators derived from arachidonic acid. LTs include the di-hydroxy acid LT (LTB₄) and the cysteinyl LTs (CysLTs; LTC₄, LTD₄ and LTE₄), all of which are involved in both acute and chronic inflammation. We and other groups identified a high-affinity LTB₄ receptor, BLT1; the LTC₄ and LTD₄ receptors, CysLT1 and CysLT2; and the LTE₄ receptor, GPR99. Pharmacological studies have shown that BLT1 signaling stimulates degranulation, chemotaxis and phagocytosis of neutrophils, whereas CysLT1 and CysLT2 signaling induces airway inflammation by increasing vascular permeability and the contraction of bronchial smooth muscle. Recently, we and other groups suggested that the LTB₄–BLT1 axis and the cysteinyl LTs–CysLT1/2 axis are involved in chronic inflammatory diseases including asthma, atopic dermatitis, psoriasis, atherosclerosis, arthritis, obesity, cancer and age-related macular degeneration using animal models for disease and gene knockout mice. This review describes the classical and novel functions of LTs and their receptors in several inflammatory diseases and discusses the potential clinical applications of antagonists for LT receptors and inhibitors of LT biosynthesis.