Major uncertainties, however, persist in the management of PAH. First, the guidelines address only adult patients with PAH and none of the other more common causes of pulmonary hypertension, such as that associated with left-sided heart disease, parenchymal lung disease, or chronic thromboembolic pulmonary hypertension. These guidelines do not address children with PAH, in whom the disease is not well studied and for which there may be different causes, responses to therapy, and side effects. Second, despite > 8,500 citations on this topic, the authors were able to assign an evidence grade to nine recommendations only. The remaining 70 were consensus-based recommendations. This highlights the dearth of high-quality, replicated clinical trials in PAH. Third, management of patients who are functional class I consists essentially of a “watchful waiting” approach. Although these patients are rare, enhanced screening in at-risk populations, such as those with scleroderma or those who are known PAH-associated mutation carriers, will identify increasing numbers of patients with early-stage PAH. Determining when and how to treat this group will require better mechanistic markers of progressive disease as well as perhaps extended drug trials to test efficacy in preventing symptomatic PAH. Such markers, which, it is hoped, will be identified by thorough, rigorous phenotyping, may also allow a more informed selection of therapy for an individual symptomatic patient with PAH; this is the so-called “personalized medicine.” Finally, the new guidelines classify all PAH medications as improving 6-min walk distance or functional class, or reducing time to clinical worsening. Notably absent are any therapeutics for the failing right ventricle. Right-sided heart failure is the major cause of death in patients with PAH,12 suggesting that the development of right ventricular-specific therapies should be a major priority in upcoming years. This will require understanding the determinants of right-sided heart structure and function in health and disease and the best tools for assessment of right-sided heart failure. These are all areas of active investigation and should bear fruit in future treatments of PAH.