Certain single severe injuries or conditions, such as the loss of two limbs or blindness, automatically result in a 100 percent disability rating. However, other injuries and illnesses can be combined to attain a 100 percent rating.

A 100% disability rating, particularly within the context of the U.S. Department of Veterans Affairs (VA) or Social Security Administration, is granted when an individual has a medical condition or a combination of conditions that are severe enough to render them totally unable to maintain "substantially gainful employment." Under VA regulations, this can be achieved through a single "total" disability, such as the loss of use of both hands or feet, total blindness, or being permanently bedridden. It can also be reached through "Schedule for Rating Disabilities" where multiple service-connected disabilities combine using "VA math" to reach a 100% total. Specific conditions that often qualify include severe Post-Traumatic Stress Disorder (PTSD) with total social and industrial impairment, advanced stages of various cancers, or chronic diseases like Parkinson's or Multiple Sclerosis that have reached a stage of total incapacitation. Additionally, "Total Disability based on Individual Unemployability" (TDIU) allows a person to be paid at the 100% rate even if their scheduled rating is lower, provided their disabilities specifically prevent them from working.