Pulmonary arterial hypertension (PAH) is a devastating and progressive disease with marked morbidity and mortality. Even though female gender represents one of the most powerful risk factors for PAH, multiple questions about the underlying mechanisms remain, and two "estrogen paradoxes" in PAH exist. First, it is puzzling why estrogens have been found to be protective in various animal models of PAH, whereas PAH registries uniformly demonstrate a female susceptibility to the disease. Second, despite the pronounced tendency for the disease to develop in women, female PAH patients exhibit better survival than men. Recent mechanistic studies in classical as well as in novel animal models of PAH, as well as recent studies in PAH patients have significantly advanced the field. In particular, it is now accepted that estrogen metabolism and receptor signaling, as well as estrogen interactions with key pathways in PAH development, appear to be potent disease modifiers. A better understanding of these interactions may lead to novel PAH therapies. It is the purpose of this review to 1) review sex hormone synthesis, metabolism, and receptor physiology, 2) assess the content in which sex hormones affect PAH pathogenesis, 3) provide a potential explanation for the observed estrogen paradoxes and gender differences in PAH, and 4) identify knowledge gaps and future research opportunities. As the majority of published studies investigated 17beta-estradiol and/or its metabolites, this review will primarily focus on estrogen effects on the pulmonary vasculature and right ventricle. Data for other sex hormones will be discussed very briefly.