Leukotrienes (LTs), including LTB(4) and cysteinyl-LTs (CysLTs) (LTC(4), LTD(4), and LTE(4)), are potent inflammatory lipid mediators which are derived from 5-lipoxygenase activity. CysLTs, which stimulate CysLT(1) and CysLT(2) receptor subtypes, are functionally involved in the pathophysiology of asthma. Selective CysLT(1) receptor antagonists are effective anti-asthmatic drugs. CysLT(1) receptor antagonists have been developed from leukotriene structural analogs, analogs of FPL 55712, a chromone carboxylic acid, and by random screening of corporate compound banks. This review will examine the biosynthesis, metabolism and mechanism of action of leukotrienes, their role in asthma, the therapeutic implications of the leukotriene pathway inhibition for asthma, and the medicinal chemistry strategies that have been exploited in the design of potent and selective CysLT(1) receptor antagonists.