Pulmonary veno-occlusive disease (PVOD) is a rare cause of pulmonary arterial hypertension (PAH). Because of the similar clinical picture of dyspnea on exertion and signs of right heart failure, PVOD is difficult to distinguish from idiopathic PAH. However, the distinction is mandatory because PVOD has a worse prognosis and, more importantly, the administration of PAH specific therapy (vasodilators) can precipitate severe acute pulmonary oedema. We present a challenging case of PAH in a patient with systemic sclerosis in whom a marked decrease in functional capacity after the initiation of bosentan therapy led to the diagnosis of PVOD. Management of PVOD patients is challenging and referral for lung transplantation should be done at the moment of diagnosis.