The paper describes the current views on the cause of a sub-class of pressure ulcers known as pressure induced deep tissue injury (DTI). A multi-scale approach was adopted using model systems ranging from single cells in culture, tissue engineered muscle to animal studies with small animals. This has led to a clear understanding on two damage mechanisms associated with the development of DTI. Direct deformation results from high, but physiologically relevant, strains and is a process that leads to the first signs of cell damage within minutes. Ischaemic damage is caused by occlusion of blood vessels, but takes several hours to develop. The paper ends with some clinical consequences.