Cell separation is a critical process for the successful growth and development of a plant. It contributes to the earliest phase of the life cycle to enable germination to take place and is a prerequisite for the softening of fleshy fruits to enable the next generation to be dispersed as seeds. In this chapter, we consider the evidence that ethylene plays a role in coordinating events associated with cell separation and the mechanisms that may be involved. Cell wall remodelling is primarily driven by the action of a cocktail of hydrolytic enzymes whose expression is spatially and temporally regulated. For phenomena such as organ abscission, ripening of climacteric fruit and aerenchyma development, there is convincing evidence that ethylene plays a regulatory role, but for cell separation at other sites this is not clear. Many of the recent breakthroughs in our understanding in this area have originated from work on the model plant Arabidopsis and the challenge is to translate these discoveries into crop species to optimize resource efficiency and make production more sustainable.