Complex molecular and cellular mechanisms are involved in the initiation and progression of hepatic fibrosis. Recent studies have shown that hepatic stellate cells, endothelin, cytokines and prostacyclin play crucial roles in this pathology. Prostacyclin exerts vasorelaxant, antioxidant and antifibrotic properties that prevent the development of fibrosis and cirrhosis in liver diseases. In this editorial, the authors discuss some of the molecular and cellular mechanisms involved in the initiation and progression of liver fibrosis and the role played by prostacyclin in counteracting it. At the moment, however, only limited information is available from clinical studies demonstrating the effectiveness of prostacyclin in liver diseases and this makes it difficult to draw any conclusions; further efforts are necessary to verify whether prostacyclin, alone or in combination with other drugs, may be a valid therapeutic option in liver diseases.