The inmates are confined for the most part of the day in single cells with facilities made of poured, reinforced concrete to deter self-harm, and are under 24-hour supervision, carried out intensively with high staff–inmate ratios.

Women classified as a "special management concern" due to violence or escape attempts are confined at Federal Medical Center, Carswell in Fort Worth, Texas.

[5] On October 22, 1983, Thomas Silverstein and Clayton Fountain, members of the Aryan Brotherhood, fatally stabbed correctional officers Merle Clutts and Robert Hoffman at the United States Penitentiary, Marion.

According to a 1998 report in the San Francisco Chronicle, Florence's main purpose is to "try and extract reasonably peaceful behavior from extremely violent career prisoners".

Silvestre Mayorqui Rivera and Richard Santiago were both charged with the first-degree murder of Manuel Torres, a high-level member of the Mexican Mafia.

Left alone with no guard supervision in the prison yard on the morning of April 21, 2005, Rivera and Santiago were videotaped brutally beating and stomping Torres to death.

Each cell contains a desk, stool, and bed, constructed almost entirely of poured concrete, as well as a toilet that shuts off if blocked, a shower that runs on a timer to prevent flooding, and a sink lacking a potentially dangerous tap.

Cells are also fitted with polished steel mirrors bolted to the wall, electric lights that can be shut off or dimmed by the inmate,[23] a radio, and a television given to inmates for good behavior; as of 2018[update], the television system included institution-run channels featuring announcements and educational courses, a number of general and specialty news and entertainment channels, and PG-rated films shown through the CCTV system.

Officers in the prison's control center monitor inmates twenty-four hours a day and can activate a "panic button", which immediately closes every door in the facility, should an escape attempt be suspected.

"H" Unit houses inmates who are members of terror groups so designated by the Department of Justice or who have had special administrative measures (SAMs) placed on them.

[34] Critics claim that the use of extended confinement in solitary cells severely affects prisoners' mental health, a conclusion supported by numerous studies.

[38] Prisoners held in Unit H are subject to special administrative measures that prevent them from communicating with journalists or privately with their own lawyers or family members.

[27] In 2020, a British District Judge refused to extradite Julian Assange to the United States on espionage charges in part because he would possibly be subjected to solitary confinement and special administrative measures at ADX.

On July 7, 2021, the High Court of Justice for England and Wales agreed to allow the United States to appeal this decision with the understanding that Assange "will not be subject to SAMs or imprisoned at ADX" if extradited.

In the 2023 fiction thriller novel Only the Dead by author and retired US Navy SEAL Jack Carr, the protagonist, James Reece, is housed in Range 13 after being suspected of an assassination attempt on a fictitious characterization of the President of the United States.

In the episode 'Svengali' from Law and Order: SVU criminal Robert Morten is transferred to ADX Florence after he masterminded several killings while already incarcerated at a less secure facility.