Out-of-proportion pulmonary hypertension (PH) is defined as an unjustified degree of PH that occurs in patients suffering from different types of parenchymal lung diseases (ie, COPD, idiopathic pulmonary fibrosis [IPF], and so forth). The concept of out-of-proportion PH was introduced quite recently in the field of PH. Until a few years ago, the term cor pulmonale was used to indicate the development of PH related to parenchymal diseases and exposure to chronic hypoxia, leading to chronic respiratory failure and, consequently, to right-sided heart failure. However, in recent years, a better understanding of the mechanisms underlying the structural remodeling of the pulmonary vascular bed has raised doubts as to whether everything can be explained by the presence of cor pulmonale. In fact, some patients may develop extremely high pulmonary artery pressure that cannot be explained solely by hypoxia and rearrangement of the pulmonary vascular bed. Due to a growing use of right-sided heart catheterization to select appropriate candidates for lung transplantation, a vast category of patients suffering from parenchymal lung diseases (often accompanied by minor pulmonary impairment on pulmonary function test and/or CT scan) with an unexplained severe degree of PH was brought to the attention of physicians. In these patients, the development of moderate to severe PH, which cannot be explained by the degree of parenchymal lung disease and hypoxia, has been termed “out-of-proportion” PH, and an arbitrary value of >35 mm Hg mean pulmonary artery pressure has been selected to identify this category of patients.