Clinical trials have remarkably changed the natural history of pulmonary arterial hypertension (PAH). Despite the relevant progresses achieved in terms of prognosis, PAH is still burned by high mortality rates, disability and low levels of quality of life. The aim of this review is to look over the history of clinical trials in PAH, starting from the little studies with prostacyclin analogues to the recent large randomized placebo-controlled trials. Moreover, the future perspectives of PAH management are addressed.