Pulmonary hypertension (PH) due to left heart failure is becoming increasingly prevalent and is associated with poor outcome. The precise pathophysiological mechanisms behind PH due to left heart failure are, however, still unclear. In its early course, PH is caused by increased left ventricular filling pressures, without pulmonary vessel abnormalities. Conventional treatment for heart failure may partly reverse such passive PH by optimizing left ventricular function. However, if increased pulmonary pressures persist, endothelial damage, excessive vasoconstriction and structural changes in the pulmonary vasculature may occur. There is, at present, no recommended medical treatment for this active component of PH due to left heart failure. However, as the vascular changes in PH due to left heart failure may be similar to those in pulmonary arterial hypertension (PAH), a selected group of these patients may benefit from PAH treatment targeting the endothelin, nitric oxide or prostacyclin pathways. Such potent pulmonary vasodilators could, however, be detrimental in patients with left heart failure without pulmonary vascular pathology, as selective pulmonary vasodilatation may lead to further congestion in the pulmonary circuit, resulting in pulmonary oedema. The use of PAH therapies is therefore currently not recommended and would require the selection of suitable patients based on the underlying causes of the disease and careful monitoring of their progress. The present review focuses on the following: (i) the pathophysiology behind PH resulting from systolic left heart failure, and (ii) the current evidence for medical treatment of this condition, especially the role of PAH-targeted therapies in systolic left heart failure.