Molecular processes underlying right ventricular (RV) dysfunction (RVD) and right heart failure (RHF) need to be understood to develop tailored therapies for the abatement of mortality of a growing patient population. Today, the armament to combat RHF is poor, despite the advancing identification of pathomechanistic processes. Mitochondrial dysfunction implying diminished energy yield, the enhanced release of reactive oxygen species, and inefficient substrate metabolism emerges as a potentially significant cardiomyocyte subcellular protagonist in RHF development. Dependent on the course of the disease, mitochondrial biogenesis, substrate utilization, redox balance, and oxidative phosphorylation are affected. The objective of this review is to comprehensively analyze the current knowledge on mitochondrial dysregulation in preclinical and clinical RVD and RHF and to decipher the relationship between mitochondrial processes and the functional aspects of the right ventricle (RV).