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Right heart failure may develop from pulmonary arterial hypertension or various forms of congenital heart disease. Right ventricular adaptation to the increased afterload is the most important prognostic factor in pulmonary hypertension and congenital heart disease, which share important pathophysiological mechanisms, despite having different aetiologies. There is substantial evidence of increased sympathetic nervous system activation in right heart failure related to both pulmonary hypertension and congenital heart disease. It is unknown to which degree this activation is an adaptive response, a maladaptive response, or if it mainly reflects disease progression. Several experimental studies and clinical trials have been conducted to answer these questions. Here, we review the existing knowledge on sympathetic nervous system activation and the effects of β-adrenoceptor blockade in experimental and clinical right heart failure. This review identifies important gaps in our understanding of the right ventricle and discusses the potential of β-blockers in the treatment of right heart failure.