In Fire with Fire following a grueling day of work, firefighter Jeremy Thomas Coleman (Josh Duhamel) and his co-workers contemplate ending the day with a refreshing drink. When Jeremy enters the liquor store to buy more alcohol, he unknowingly witnesses the clerk being brutally murdered at the hands of Hagan (Vincent D'Onofrio), a white nationalist. After Jeremy narrowly escapes with his life, police detective Mike Cella (Bruce Willis) learns of Hagan’s recent crime and takes an interest in the case. Hagan is arrested and Jeremy identifies him in a line up; however, Hagan demonstrates that he knows full well that Jeremy is behind the two-way mirror by reciting Jeremy's(Fire with Fire) full name, address and social security number.
Prior(Fire with Fire) to the trial, Jeremy is forced to change his name to Jeremy Douglas and surrender his entire career as he is placed into the witness protection program. Although Jeremy finds it difficult to cope with the loss of his career, he also finds consolation in his budding romance with Talia Durham (Rosario Dawson), a Deputy United States Marshal assigned to his case.
Later, Hagan’s(Fire with Fire) attorney (Richard Schiff) arranges for him to be released from prison in the weeks leading up to the trial. As a result, Jeremy and Talia find their lives in jeopardy. When Talia is severely wounded by one of Hagan’s men, Jeremy flees from the witness protection program and travels to Long Beach, CA. There, Jeremy teams up with one of Hagan’s rival gangs in order to bring him down. Soon, Jeremy will have to work to eliminate Hagan’s men one by one in order to protect the woman he loves(Fire with Fire).