Objective: To present a historic perspective and an up-to-date understanding of the involvement of cysteinyl-leukotrienes (cys-LTs) in asthmatic airway smooth muscle (ASM) cell hyperplasia., Data Sources: Data collected from human tissues, from animal models of airway inflammation, and from ASM cells cultured in vitro are included., Study Selection: All studies regarding the potential contribution of cys-LTs on ASM cell hyperplasia are reviewed., Results: Whereas in vivo observations are consistent and seem to attribute an important role for cys-LTs in ASM cell hyperplasia, the observations made in cultured ASM cells are inconsistent, with studies documenting a mitogenic potential only reporting marginal effects., Conclusion: This dichotomy between in vitro and in vivo results led to the elaboration of a hypothesis suggesting that the mitogenic effect of cys-LTs on ASM cells may be indirect and mediated by a paracrine loop involving transforming growth factor beta1 production by airway resident and inflammatory cells.