Mitochondria exist as a highly dynamic tubular network, and their morphology is governed by the delicate balance between frequent fusion and fission events, as well as by interactions with the cytoskeleton. Alterations in mitochondrial morphology are associated with changes in metabolism, cell development and cell death, whilst several human pathologies have been associated with perturbations in the cellular machinery that coordinate these processes. Mitochondrial fission also contributes to ensuring the proper distribution of mitochondria in response to the energetic requirements of the cell. The master mediator of fission is Dynamin related protein 1 (Drp1), which polymerises and constricts mitochondria to facilitate organelle division. The activity of Drp1 at the mitochondrial outer membrane is regulated through post-translational modifications and interactions with mitochondrial receptor and accessory proteins. This review will concentrate on recent advances made in delineating the mechanism of mitochondrial fission, and will highlight the importance of mitochondrial fission in health and disease. This article is part of a Special Issue entitled: Mitochondrial dynamics and physiology.