Acquitted after a four-year trial that ended in 2013, prosecutors hope they can successfully prosecute the two in a bid to establish a judicial link between Belgrade's then-government and the wartime atrocities in Bosnia.
Two former Serbian secret policemen went on trial for a second time on Tuesday over their alleged role in the ethnic cleansing of thousands of non-Serbs during the Balkan conflicts of the 1990s.
The initial four-year trial of Jovica Stanisic, the former head of Serbia's State Security Service (DB) and Franko Simatovic, his alleged right-hand man, resulted in an acquittal in 2013, but an appeals judge ordered a retrial.
The trial is seen as the last remaining case that could establish a judicial link between late Yugoslav President Slobodan Milosevic's Belgrade government and atrocities committed in Bosnia during the 1992-95 war that followed the collapse of multi-ethnic Yugoslavia.
Stanisic and Simatovic are accused of having "established, trained, armed, supported and directed" some of the most notorious Serb militias, including the groups known as the "Scorpions" and "Arkan's Tigers."
The pair, who both deny the charges, played a leading role in efforts to create "ethnically homogeneous and Serb-dominated areas" in Bosnia and Croatia, UN prosecutor Douglas Stringer told the court at the opening of the hearings.
"These accused made those crimes happen by their direction and their unflagging support of the Serb troops they used" to reach their goal, he said.
The aim was to create exclusively Serb territories in regions that had been ethnically mixed for generations by violently driving out non-Serbs, he added.
The pair were acquitted at their first trial, the UN court ruling there was no evidence that any orders they issued were "specifically directed" at aiding the commission of the crimes.
Appeals judges rejected the lower court's reasoning and ordered the retrial.