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The relentlessly beating heart has the greatest oxygen consumption of any organ in the body at rest reflecting its huge metabolic turnover and energetic demands. The vast majority of its energy is produced and cycled in form of ATP which stems mainly from oxidative phosphorylation occurring at the respiratory chain in the mitochondria. Apart from energy production, the respiratory chain is also the main source of reactive oxygen species and plays a pivotal role in the regulation of oxidative stress. Dysfunction of the respiratory chain is therefore found in most common heart conditions. The pathophysiology of mitochondrial respiratory chain dysfunction in hereditary cardiac mitochondrial disease, the ageing heart, in LV hypertrophy and heart failure, and in ischaemia-reperfusion injury is reviewed. We introduce the practising clinician to the complex physiology of the respiratory chain, highlight its impact on common cardiac disorders and review translational pharmacological and non-pharmacological treatment strategies., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)