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Mitochondrial dynamics shape the mitochondrial network and contribute to mitochondrial function and quality control. Mitochondrial fusion and division are integrated into diverse cellular functions and respond to changes in cell physiology. Imbalanced mitochondrial dynamics are associated with a range of diseases that are broadly characterized by impaired mitochondrial function and increased cell death. In various disease models, modulating mitochondrial fusion and division with either small molecules or genetic approaches has improved function. Although additional mechanistic understanding of mitochondrial fusion and division will be critical to inform further therapeutic approaches, mitochondrial dynamics represent a powerful therapeutic target in a wide range of human diseases.