He was the right-hand man of Serb wartime leader Radovan Karadzic and speaker of the separatist Bosnian Serb parliament.
Mr Krajisnik earned the nickname "Mr No" for his uncompromising stance in peace negotiations during the 1992-1995 war.
His power was sometimes said to equal that of Mr Karadzic.
During their leadership, Serb forces laid siege to Sarajevo and purged Muslim and Croat populations from Serb-held territory.
They also overran two UN-designated "safe areas", executing hundreds of unarmed men trying to flee the enclave of Srebrenica.
Like other leaders in the Bosnian conflict, Mr Krajisnik is rumoured to have enriched himself through illegal dealings during and after the war.
Pious
Mr Krajisnik, called Momo by his friends, was one of the first members of the nationalist Serb party, SDS, when it was formed in 1990.
He was speaker of the Bosnian parliament from 1990 to 1992, before the war began.
After the war, he served as the Serb representative on the three-member Bosnian presidency, along with a Croat and a Muslim.
But analysts say he largely used the position to thwart any reintegration between Bosnian Serb and Muslim-Croat entities in Bosnia.
His early post-war strength was said to stem from his control of the hardline police and municipal authorities.
But he lost his bid for re-election in 1998 to a relatively moderate Serb leader, Zivko Radisic.
His aides say he is a pious man, who considers separation based on ethnicity and religion to be natural.
But Amor Masovic, head of the Muslim commission for missing persons, described him as "one of the masterminds of the genocide and ethnic cleansing in Bosnia".
Embezzlement
Mr Krajisnik, a widower and father of three, came from a well-off farming family just outside Sarajevo.
After studying economics he joined a state-owned firm, Energoinvest, where he rose to become finance director of a unit making parts for nuclear reactors.
In 1983, Mr Krajisnik was convicted of embezzling Energoinvest funds, but was exonerated by a higher court after serving eight months in jail.
Mr Krajisnik said he had been persecuted for championing the Serb national cause against Bosnian Muslims and Croats who wanted to preserve Bosnia as a multi-ethnic republic.