Ratko Mladic, the former Former Bosnian Serb army commander, faces 11 counts of war crimes and crimes against humanity, including genocide.
The charges relate to 1992-95 Bosnian war.
Prosecutors on the opening day of this trial, said he intended to “ethnically cleanse” Bosnia.
At the one point, he is reported to have signalled at the gallery with his finger across his throat – the sign used by Serb death squads to UN peacekeepers before entering Muslim villages.
He is accused of orchestrating the massacre of more than 7,000 Bosniak (Bosnian Muslim) boys and men at Srebrenica in 1995.
He is also charged in connection with the 44-month siege of Sarajevo during which more than 10,000 people died.
Prosecuting counsel Dermot Groome said:”Four days ago marked two decades since Ratko Mladic became the commander of the main staff of the army of Republika Srpska – the VRS.
“On that day, Mladic began his full participation in a criminal endeavour that was already in progress. On that day, he assumed the mantle of realising through military might the criminal goals of ethnically cleansing much of Bosnia. On that day, he commenced his direct involvement in serious international crimes.”
Mr Groome said that by the time Gen Mladic and his troops had “murdered thousands in Srebrenica”, they were “well-rehearsed in the craft of murder”.
He then showed judges video of the aftermath of a notorious shelling of a market in the Bosnian capital Sarajevo, in which dozens of people died.
Mladic has called the accusations “monstrous.”
The court has entered a not guilty plea on his behalf.