Pulmonary arterial hypertension (PAH) is a progressive disease characterised by 
remodelling of small pulmonary arteries leading to an increased pulmonary 
vascular resistance, right ventricular failure and death. Available treatments 
try to re-establish the equilibrium on three signalling pathways: the 
prostacyclin, the endothelin (ET)-1 and the nitric oxide. Prostanoids, such as 
epoprostenol or treprostinil have a vasodilator, antiproliferative and 
immunomodulatory effect and, despite the administration inconveniences, 
represent established therapies for severe cases of PAH. Recently oral 
prostacyclin receptor agonists have shown encouraging results. Many clinical 
studies targeting the vasoconstrictor ET-1 pathway with receptor antagonists 
like bosentan and ambrisentan have shown strong results, even more optimism 
coming from macitentan, the newest drug. Sildenafil and tadalafil, two 
phosphodiesterase type-5 inhibitors, have shown improved exercise capacity by 
increasing the nitric oxide level. Riociguat, acting on the same nitric oxide 
pathway, as a guanylatecyclase activator, has shown promising results in 
clinical trials and will be available soon. Long-awaited results for 
tyrosin-kinase inhibitor, imatinib, as an antiproliferative therapy in PAH have 
been disappointing, due to severe adverse events. In conclusion, although it 
remains a disease with severe prognosis, the past 20 years have represented a 
huge progress in terms of treatments for PAH with interesting opportunities for 
the future.