As in every tissue, the metabolism of xenobiotic compounds in pulmonary tissues is both complex and often cell specific and selective. Despite years of research the precise mechanisms and factors that determine pulmonary-specific metabolism and associated consequences for xenobiotic disposition in humans remain relatively undefined. Several excellent reviews dedicated to this topic were highlighted in the previous version of this chapter [1–9]. While dated, these authoritative reviews remain highly relevant to the field. A more up to date review has recently been published [10]. When possible, additional sub-topic specific reviews are referenced throughout the sections of this updated chapter.