Severe pressure ulcers and deep tissue injury are associated with higher mortality rates, longer hospital stays, and costly treatment. Time is a critical factor in commonly employed measures (eg, pressure redistribution for wheelchair users and patient turning schedules) to prevent pressure ulcers and deep tissue injury. Surprisingly, information regarding the timeframe for pressure ulcer onset, particularly for deep tissue injury onset, is scant. To create a timeframe for the development of pressure ulcers and deep tissue injury, available evidence from the following study types was obtained and reviewed: 1) studies involving patients who underwent surgeries of known duration and subsequently developed a serious pressure ulcer with subcutaneous tissue damage or deep tissue injury; 2) animal studies in which loads were applied on soft tissues of anesthetized animals and tissue viability monitored in real time or using histology post-euthanasia; and 3) in vitro models in cell cultures and tissue-engineered constructs. Findings from the three models indicate that pressure ulcers in subdermal tissues under bony prominences very likely occur between the first hour and 4 to 6 hours after sustained loading. However, research examining these timeframes in sitting patients is not available. Further fundamental research, employing animal and cell culture models, is required to narrow this range further and to correlate the time factor to the extent of tissue damage.