Abstract Dehydroepiandrosterone (DHEA) is a steroid hormone derived from cholesterol synthesized by the adrenal glands. DHEA and its 3β-sulphate ester (DHEA-S) are the most abundant circulating steroid hormones. In human, there is a clear age-related decline in serum DHEA and DHEA-S and this has suggested that a relative deficiency in these steroids may be causally related to the development of a series of diseases associated with aging including cardiovascular diseases (CVD). This commentary aims to highlight the action of DHEA in CVD and its beneficial effect in therapy. We thus discuss the possible impact of serum DHEA decline and DHEA supplementation in diseases such as hypertension, coronary artery disease and atherosclerosis. More specifically, we provide evidence for a beneficial action of DHEA in the main disease of the pulmonary circulation: pulmonary hypertension. We also examine the potential cellular mechanism of action of DHEA in terms of receptors (membrane/nuclear) and associated signaling pathways (ion channels, calcium signaling, PI3K/AKT/eNos pathway, cGMP, RhoA/RhoK pathway). We show that DHEA acts as an anti-remodeling and vasorelaxant drug. Since it is a well-tolerated and inexpensive drug, DHEA may prove to be a valuable molecule in CVD but it deserves further studies both at the molecular level and in large clinical trials.