The introduction of specific drugs for the treatment of pulmonary arterial hypertension over the last 20 years has led to an improvement of clinical and hemodynamic conditions and prognosis of affected patients. The use of combination therapy has made it possible to act simultaneously on several biological pathways involved in the etiopathogenesis of the disease. However, although the diagnosis and management have radically changed in recent years, the disease remains progressive and often fatal. The purpose of this paper is to review and discuss the results of the main clinical trials and the future perspectives of combination strategies for the treatment of pulmonary arterial hypertension.