He is the co-author with David Corn of the book titled Russian Roulette: The Inside Story of Putin's War on America and the Election of Donald Trump, published on March 13, 2018.

Isikoff had been prepared to break the Clinton–Lewinsky scandal, but several hours before going to print, the article was killed by top Newsweek executives.

[9] In the May 9, 2005, issue of Newsweek, Isikoff co-wrote an article that stated that interrogators at Guantanamo Bay "in an attempt to rattle suspects, flushed a Quran down a toilet."

Detainees had earlier made similar complaints, but this was the first time a government source had appeared to confirm the story.

The article caused widespread rioting and massive anti-American protests throughout some parts of the Islamic world, resulting at least 17 deaths in Afghanistan.

The magazine later retracted the story after noting that the anonymous official who was their source subsequently could not remember important details.

Isikoff allegedly refused, saying he didn't want to take possession of stolen property and did not have access to President Bill Clinton's DNA to test the evidence on the dress anyway.

News with colleagues, Isikoff uncovered a CIA plot to kidnap Julian Assange from the Ecuadorian embassy in London, though the plan was reportedly never approved.