Bosnian Serb army commander Ratko Mladic is set to go on trial on 11 counts of war crimes and crimes against humanity, including genocide.
He is the last of the main protagonists in the Balkan wars of the 1990s to face an international trial in The Hague.
He is accused of orchestrating the week-long massacre of over 7,000 Muslim boys and men at Srebrenica in 1995.
General Mladic calls the accusations "monstrous" and the court has entered a "not guilty" plea on his behalf.
Now nearly 70, Gen Mladic spent 15 years on the run before being apprehended by Serb forces last May and sent to The Hague.
He has been awaiting trial in the same prison as his former political leader Radovan Karadzic, who was arrested in 2008 and is now about halfway through his trial on similar charges to Gen Mladic.
Judicial authorities have rejected defence calls to delay proceedings, most recently a petition to have the Dutch presiding Judge Alphons Orie replaced on grounds of alleged bias.
The number of crimes of which Gen Mladic - who is in frail health - stands accused has been almost halved to speed up his trial.
Gen Mladic is accused of committing genocide and other crimes against Bosnian Muslims and Croats in a brutal campaign of ethnic cleansing that began in 1992 and climaxed in Srebrenica in 1995.
Then, Serb fighters overran the Srebrenica enclave in eastern Bosnia - supposedly under the protection of Dutch UN peacekeepers. Men and boys were separated off, shot dead and bulldozed into mass graves - later to be dug up and reburied in more remote spots.
Gen Mladic is also charged over the 44-month siege of Sarajevo during which over 10,000 people died.
These were the worst atrocities in Europe since the end of World War II, says the BBC's world affairs correspondent Peter Biles in The Hague.
Over 200 hours, the prosecution will make its case against Mladic, taking testimony from over 400 witnesses.
Pre-trial hearings have been characterised by ill-tempered outbursts from Gen Mladic, who has heckled the judge and interrupted proceedings.
"The whole world knows who I am," he said at a hearing last year.
"I am General Ratko Mladic. I defended my people, my country... now I am defending myself."
The case has stirred up strong emotions among watching survivors, with some shouting "murderer" and "killer" from the court gallery.
Many fear that Gen Mladic, who suffered at least one stroke while in hiding and remains in frail health, could escape judgement by dying mid-trial.
The architect of the Balkan wars, former Serbian President Slobodan Milosevic, died in detention in his cell in 2006, before receiving a verdict.