The 63-year old former commander of the Bosnian Serb troops had been on the run from international justice since he was charged by the International Criminal Tribunal for the former Yugoslavia (ICTY) in 1995, together with Bosnian Serb political leader Radovan Karadzic. Karadzic is still at large.
The indictment against Mladic details his role the 1992-95 war in Bosnia, the bloodiest of the conflicts in the Balkans in the 1990s which left over 200,000 people dead.
The document details how Mladic went from being an commander in the Yugoslav army in 1991 to becoming the commander of the main staff of the Bosnian Serb army shortly after the Bosnian Serbs proclaimed their own republic inside Bosnia.
In particular the indictment details Mladic's role in the 44-month siege of Sarajevo, the campaign of ethnic cleansing throughout Bosnia and holding dozens of UN peacekeepers hostage.
He is charged with being a member of a criminal enterprise whose objective was "the elimination or permanent removal ... of Bosnian Muslim, Bosnian Croat and other non-Serb inhabitants from large areas of Bosnia-Hercegovina through the commission of crimes".
The two counts of genocide, the gravest of war crimes, focus on the so-called ethnic cleansing campaign aimed at driving out Muslims by force or terrorizing them into fleeing from Serb dominated parts of Bosnia.
The indictment cites specifically the establishment of camps and detention centres for Bosnian Muslims and the 1995 Srebrenica massacre.
Thousands of people were held in horrific living conditions in the camps run by Bosnian Serbs at the start of the 1992-95 war.
In the Prijedor area alone, more than 1,500 people died in the notorious camps of Omarska, Trnopolje and Keraterm.
Conditions in the camps were "calculated to bring about physical destruction", detainees were subjected to "torture, sexual violence and beatings" and faced "inhumane living conditions", the prosecution has said.
In July 1995, Serb troops overran the UN-protected enclave of Srebrenica in eastern Bosnia and killed almost 8,000 Muslim men and boys in the deadliest single bloodbath in Europe since World War II.
The appeals chamber of the International Criminal Tribunal for the former Yugoslavia (ICTY) confirmed in 2004 that the massacre was genocide.
They convicted Bosnian Serb general Radislav Krstic, who led the assault on the town together with Mladic himself, for aiding and abetting genocide and sentenced him to 35 years.
In all Mladic faces 15 charges also including persecutions, extermination and murder, deportation, inhumane acts, unlawfully inflicting terror on civilians and taking of hostages.
Others on the run
Serbian general Vlastimir Djordjevic is on the run from charges of war crimes committed in Kosovo during the 1998-99 Serb crack-down on the province.
Bosnian Serb general Zdavro Tolimir stands accused of war crimes and crimes against humanity for the 1995 Srebrenica massacre in Bosnia.
Among those already arrested and awaiting transfer to the tribunal are another Bosnian Serb, Dragan Zelenovic, charged with the rape and murder of Muslim teenagers in Foca, Bosnia, was arrested in Russia on August 30. He is awaiting transfer to the UN court in The Hague.