Leukotrienes (LT) comprise a group of biologically highly potent lipid mediators synthesized by 5-lipoxygenase from 20-carbon polyunsaturated fatty acids, predominantly arachi-donate (1–3). They include the cysteinyl LT, LTC4, LTD4, LTE4, representing biologically active constituents of the long-known “slow-reacting substance of anaphylaxis” and the dihy-droxyeicosatetraenoate, LTB4. LT act at nanomolar concentrations in intercellular communication, signal transduction and on host defense. Extensive studies during the last years have demonstrated that LT are not only locally acting mediators but also systemically acting substances.Recent progress in LT research has led to a more detailed understanding of their biosynthesis, degradation, and inactivation. Moreover, the pathogenetic role of LT in various human diseases has become recognized, and inhibitors of biosynthesis as well as receptor antagonists interfering with signal transduction were developed.The aims of the review are1) to update the current knowledge of the synthesis, metabolism, and principal role of LT as mediators under physiologic and pathologic conditions;2) to give a brief overview about the development, state of the art, and limitations of analytical techniques;3) to discuss clinical conditions with particular emphasis on pediatric diseases in which LT are assumed to play a pathobiologic role;4) to illustrate how present knowledge has influenced current pathophysiologic concepts; and5) to briefly present future aspects of biochemical and clinical research on LT.