Glutathione is one of the most abundant proteins in vivo involved in maintaining cellular homeostasis and is essential for the regulation of oxidant stress. Gamma-Glutamyl transferase (GGT) is the first enzyme of the gamma glutamyl cycle that regulates the antioxidant glutathione, hence it is a critical enzyme in glutathione homeostasis. Recent findings have indicated upregulation of GGT in inflammation, increasing antioxidant defence whilst potentially driving leukotriene-induced inflammation. GGT is a marker of future comorbid diseases consistent with inflammation (and oxidative stress) as a key central pathophysiological process. COPD reflects several distinct pathological phenotypes. Inflammation (and hence oxidative stress) is influenced by other factors such as bacterial colonisation and exacerbations. The increased incidence of other co-morbid conditions with systemic inflammation suggests that common pathophysiological processes are responsible. Active oxidant stress and hence the role of GGT may play a role in these processes. Future studies of systemic and local GGT function and genotypes in well characterised patients may lead to a better understanding of the processes involved and hence the development of new treatment strategies.