1. Antipsoriatic anthrones are among the most commonly used topical agents for the treatment of psoriasis. 2. These drugs generate reactive oxygen species during their auto-oxidation under physiological conditions. 3. Recent studies have indicated that activation of molecular oxygen by anthrones may play a critical role in their mechanism of action at the molecular level. 4. This article summarizes the evidence pointing toward the significance of oxygen activation and radical formation in the antipsoriatic action and induction of skin inflammation of anthrones. 5. Also, the role of oxygen radical formation in the development of novel anthrones devoid of inflammatory and staining properties is discussed.