While the role of the adrenergic nervous system in the progression of left ventricular failure has been well established, its contribution to the pathogenesis of pulmonary arterial hypertension (PAH) and the resultant right ventricular failure is far less clear. The earliest attempts to treat PAH included drugs that were α-adrenergic agonists such as tolazoline [1] and isoproterenol [2]; unfortunately, their administration usually resulted in systemic hypotension and little evidence of a beneficial effect on pulmonary circulatory or right ventricular dynamics. More recently, interest has shifted towards targeting the β-adrenergic pathway as a therapeutic strategy for PAH. Nebivolol, a β₁ antagonist and β_2–3 agonist, inhibits proliferation of pulmonary vascular cells and produces endothelial and nitric oxide-dependent relaxation of pulmonary artery rings [3]; both nebivolol and pulmonary artery sympathetic denervation (PADN) attenuate vascular remodelling in monocrotaline-treated rats [3, 4], and single-centre preliminary results of PADN in PAH patients are of considerable interest [5]. In this issue of the European Respiratory Journal, van Campen et al. [6] report the results of their single-centre study of the effects of β-adrenergic blockade in patients with PAH. Their results reinforce the notion that the pulmonary and systemic circulations and their respective ventricles behave very differently both in the pathogenesis of disease states and in response to targeted therapies.