The history of leukotriene (LT) research has been documented in numerous articles and reviews since the discovery of the LT biosynthetic pathway1 and the delineation of the various chemical structures involved in the pathway and their total synthesis.2 Three previous Perspective articles have provided periodic updates, the first in 1981,3 the second 1 decade later covering LT receptor antagonists,4 and the third in 1992 covering LT biosynthesis inhibitors.5 With this background, the task of this Perspective is to update the status of LT intervention research by providing an overview of the leading enzyme inhibitors and receptor antagonists as well as the status of clinical trials with these agents and how the latter are influencing the development of new therapeutic modalities for the treatment of inflammation and allergy. The clinical proof-of-concept for LT intervention has taken longer than expected considering that the biosynthesis and chemical composition of LTs were delineated by 1979. It is now clear that LT intervention therapy represents a promising new modality for the treatment of asthma. Several compounds including the 5-lipoxygenase (5-LO) inhibitor zileuton (1) and the cysteinyl LT antagonist zafirlukast (2) have completed pivotal clinical trials, while several other LT modulators are progressing to this stage. Within a few years the therapeutic potential of these new agents in asthma and other inflammatory and allergic disorders will be evident.