Mitochondrial morphology is a crucial determinant of mitochondrial and cellular function. Opposing fusion and fission events shape the tubular mitochondrial reticulum and ensure mitochondrial transport within cells. Cellular stress and pathophysiological conditions can lead to fragmentation of the mitochondrial network, which facilitates mitophagy and is associated with cell death. However, mitochondrial shape changes are also intertwined with the cellular metabolism, and metabolic switches can induce but also result from alterations in mitochondrial morphology. Here, we discuss recent advances in the field of mitochondrial dynamics, demonstrating cell- and tissue-specific effects of mitochondrial fragmentation on cellular metabolism, cell survival, and mitochondrial quality control.