Glutathione S-transferases (GSTs) constitute a super family of dimeric phase II metabolic enzymes that catalyze the conjugation of reduced glutathione with various electrophilic compounds and reactive oxygen species (ROS). Failure to detoxify ROS, as a sequel of altered GST genotype is able to aggravate the inflammatory cascade, promote bronchoconstrictor mechanisms, activate asthma-like symptomatology, and hamper lung development. Intriguingly, the same GST genotype can aggravate or improve physiological traits and maturation of respiratory system, from gestation to late adulthood. This article attempts to unravel the complex interaction of GST's genetic variations with "inner" and "outer", polymorphic and erratic, human environment (tobacco smoke, urban pollution, workplaces, and in utero status). Considering that these variations are very frequent among ethnicities and that GSTs play a part in respiratory system formation and maturation, they appear to be of great interest for the clinician and the researcher in this field.