Sustained deformations were identified as inflicting the primary cell and tissue damage which results in pressure ulcers. Sustained deformations are causing cell distortions that within 10s-of-minutes affect cytoskeletal integrity and function. This leads to plasma membrane poration which, consequently, gives rise to abnormal transport across the plasma membrane. The inevitable outcome is loss of cell homeostasis which occurs en mass, and is followed by necrotic and apoptotic cell death, an inflammatory response and, eventually, macroscopic spread of the damage across different tissue layers. The above has important implications on the design and evaluation of medical devices used for pressure ulcer prevention such as mattresses and wheelchair cushions, and also on the risk for medical device-related pressure ulcers from other diagnostic and treatment devices which are in potential contact with the skin. In a nutshell, the basic science findings point to a requirement that all devices should be designed or used so that the tissue deformations produced in skin and deeper tissues would be minimal and adequately distributed. The lecture will describe the cell-scale damage in the onset of pressure ulcers from a mechanobiological perspective, and will review the experimental work conducted to characterize the cell injury cascade. The implications on the design and evaluation of medical devices and equipment will be reviewed as well.