PURPOSE OF REVIEW: The cause of interstitial lung diseases (ILDs) such as lung fibrosis or sarcoidosis is still largely unknown. Pharmacotherapeutic treatment in ILD lacks a firm mechanistic molecular basis. A striking paradox is that ILDs result in a shortage of oxygen and that at the same time reactive oxygen species are responsible for the tissue damage in ILDs. The realization of the importance of reactive oxygen species offers new possibilities for therapeutic interventions. RECENT FINDINGS: Remarkably, the two drugs that have been shown to be the most effective ones in the treatment of lung fibrosis are in fact antioxidants that protect against the toxicity of oxygen. Redox cycling drugs that are notorious oxygen radical generators may also cause ILD. Apart from lung fibrosis, sarcoidosis also has recently been associated with the occurrence of oxidative stress. SUMMARY: The limited number of ILD patients necessitates multicenter trials to obtain enough power to reach clinically relevant data. The specific fibrotic toxicity of O2 might be a lead in the development of new therapies and of suggesting optimal antioxidant dietary regimes.