This perspective on Meireles et al. (beginning on p. 707 in this issue of the journal) discusses the increasing evidence for the role of female steroid hormones in lung cancer development and progression. The novel work of Meireles et al. is the first evidence for the rapid upregulation by tobacco smoke of a key cytochrome P450 gene that can metabolize estrogens such as β-estradiol to potentially carcinogenic catechol and quinine forms, as well as the first evidence for the colocalization of β-estradiol and estrogen receptors in murine airway epithelium. Actions of estrogens that contribute to lung carcinogenesis, especially in the presence of tobacco smoke, may involve both reactive intermediates that damage DNA and steroid hormone receptor signaling that promotes growth.