Mladic, 70, faces 11 overall counts for genocide, war crimes and crimes against humanity which include masterminding the massacre of almost 8,000 men and boys at Srebrenica in 1995.
Dressed in a dark grey suit and dark tie, Mladic applauded as the judges walked in before the International Criminal Tribunal for the former Yugoslavia.
Prosecutors also hold him responsible for the 44-month siege of Sarajevo where his forces waged a "terror campaign" of sniping and shelling which left 10,000 civilians dead.
It was in pursuit of a "Greater Serbia" that Mladic allegedly ordered his troops to "cleanse" Bosnian towns, driving out Croats, Muslims and other non-Serbs.
Dubbed the "Butcher of Bosnia", Mladic was arrested in northeastern Serbia in May last year after 16 years on the run, wanted by the tribunal for his role in Bosnia's 1992-95 war which left 100,000 dead and 2.2 million homeless.
Mladic has pleaded not guilty to the charges in a trial that could last up to three years. If found guilty, he could face life behind bars.
Former Bosnian Serb political leader Radovan Karadzic is already on trial before the tribunal.