Prostacyclins have a favourable pharmacological profile for treatment of pulmonary hypertension as they possess vasodilative, antiproliferative, antiaggregatory, and anti-inflammatory properties that may compensate the main pathologic changes in the small pulmonary arteries. In severe pulmonary hypertension these vessels show a deficit in the endogenous prostacyclin secretion. The therapeutic potential of prostacyclin for pulmonary hypertension has been known since 30 years, and since nearly 20 years prostacyclin has been approved for idiopathic PAH. There are intravenous, subcutaneous, and inhaled approaches of different substances who share many but not all pharmacologic properties. However, none of these approaches are easy and free of adverse effects. Long-term experience and careful decision-making are instrumental to achieve favourable clinical long-term results.