Pulmonary veno-occlusive disease is a rare cause of pulmonary hypertension which is part, together with pulmonary capillary hemangiomatosis, of the special designation (subgroup 1’) within pulmonary hypertension group 1 in the latest classification of the pulmonary hypertension World Symposium. Recent discovery that gene mutations in eukaryotic translation initiation factor 2 alpha kinase 4 (EIF2AK4) are responsible for inherited forms of pulmonary veno-occlusive disease has changed the role of genetic testing, acquiring relevant importance in the diagnosis of these patients. Despite the advances in genetic, cellular and molecular basis knowledge in the last decade, pulmonary veno-occlusive disease remains as a rare aetiology of pulmonary hypertension without any effective medical treatment approved and poor outcomes. This document aims to review the advances occurred in the understanding of pulmonary veno-occlusive disease in the last years.