Many lines of independent research have pointed out the role of oxidative stress as a fascinating pathogenic link between the three main hallmarks of systemic sclerosis (SSc), viz. humoral and cellular immunity activation, microvascular damage and widespread tissue fibrosis. Therefore counteracting oxidative stress may have a favourable impact on clinical features and progression of disease. It is becoming clearer that Iloprost, a synthetic stable analogue of prostacycline, currently employed in the treatment of SSc vascular features, also possess anti-oxidative properties beside its prostaglandin-like vasodilatory and antiaggregant effects. This brief review is aimed to discuss available clinical evidences supporting Iloprost antioxidant action and focus on putative molecular pathways underlying it.