The pathological features of pulmonary arterial hypertension are highlighted in this review, which can serve as a guide to diagnosis and identification of potential cellular targets for novel lines of therapy. It also emphasizes the variability of pathological processes found in pulmonary hypertensive lungs collected by the Pulmonary Breakthrough Initiative of the Cardiovascular Medical Research Fund. This initiative is aimed at banking properly phenotyped lung tissue and implementing relevant human lung-based investigations of pulmonary arterial hypertension. This effort has led to an insight of site-specific heterogeneity of relevant pulmonary vascular pathologies and how associated histopathological processes, including interstitial fibrotic and inflammatory findings, may need to be considered in the development of future therapies. We also highlight the pulmonary vascular pathology in schistosomiasis-associated pulmonary arterial hypertension, possibly the most frequent cause of pulmonary hypertension worldwide.