Karadic is a leader of the Bosnian Serbs, and former President of the Bosnian Serbian Republic. He is a leader of the "Serbian Democratic Party" of Bosnia, which was founded in February 1992.

Since the war began in April 1992, Karadic has signed several "Peace Plans" including the Vance-Owen Peace Plan, in 1993. However, he has been openly defiant against the Dayton Peace Accords, which were signed on behalf of the Serbs by the Serbian leader Milosevic.

Karadic (or “Karadzic”) is responsible for determining military strategy and negotiating on behalf of Bosnian Serbs. In July 1995, the United Nations war crimes tribunal indicted Karadic, Mladic, and 22 other Serbs for genocide and crimes against humanity including ethnic cleansing. Very few of these people have actually been captured, although during late August, 1997, there were rumors of an impending NATO arrest-raid on his HQ. During 1997 Karadic experienced increasing opposition to his hard-line Pale government from the person who succeeded him as President of the Bosnian Serb Republic, Biljana Plasvic, and a power struggle ensued. Geographically, Plasvic controls the northern half around her power base of Banja Luka, and Karadzic the eastern part under Pale.