Riociguat has been approved for use in adults with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension. No clinical data on its therapeutic use in children with PAH are currently available. We report the case of a now four-year-old boy who initially presented at the age of 10 months with suprasystemic pulmonary hypertension (PH) and right ventricular (RV) failure, vomiting, peripheral cyanosis, and failure to thrive. Cardiac catheterization revealed severe PAH. At radiologic suspicion of interstitial lung disease, repeated CT scan and an open lung biopsy were performed but could not clarify the entity of PAH. Given the demonstrated vasoreactivity, the boy was started on the calcium channel blocker amlodipine, in combination with the endothelin-1 receptor antagonist bosentan. Two years later, based on persistently systemic PAH with lost vasoreactivity, PAH therapy was changed to bosentan and phosphodiesterase-5 inhibitor sildenafil . . . .