Prostacyclin and its analogues (prostanoids) are potent vasodilators, and exhibit antithrombotic, antiproliferative and anti-inflammatory properties. Pulmonary arterial hypertension (PAH) is characterised by vasoconstriction, thrombosis and proliferation, and is associated with reduced synthesis of endogenous prostacyclin. This provides a strong rationale for the use of prostanoids to treat PAH, a concept that is now supported by more than two decades of clinical research and experience. Intravenous and subcutaneous prostanoids have clearly demonstrated efficacy in severe PAH, but adverse events related to the drug delivery system, systemic side-effects and tachyphylaxis have driven research into alternative prostanoid treatments. Iloprost is administered by inhalation, and thus avoids most of the systemic side-effects associated with i.v. or subcutaneous prostanoid infusion. Two randomised controlled 12-week trials in patients with PAH have demonstrated efficacy and a favourable safety profile for iloprost as monotherapy (the AIR trial) and in combination with oral bosentan (STEP). Open-label uncontrolled long-term studies of inhaled iloprost therapy indicate that this treatment may improve long-term outcomes in PAH.