Pulmonary arterial hypertension is an orphan disease and a model for drug developments over recent years. Expert centers have focused basic science on the pulmonary vasculature and the right ventricle, followed by a direct transfer of innovative concepts to clinical research. Successful examples for translational experimentation are the endothelin receptor antagonists, prostacyclin receptor agonists, and the activators of soluble guanylate cyclase. On the other hand, there have been failures such as vasoactive intestinal peptide, statins, and escitalopram. Several new drugs and gene therapy are under investigation, thus significant advances are anticipated.