The 54-year-old Bhutto returned from eight years of exile in October following a deal to drop corruption charges stemming from a previous stint as prime minister, and had announced her candidacy for Pakistan's parliamentary elections.
The attack, after an outdoor rally in Rawalpindi, killed at least 16 other people and left her popular Pakistan People’s Party (PPP) in disarray ahead of the scheduled voting.
But Bhutto's absence will also be felt outside Pakistan's borders, given South and Central Asia's political history and the threat that extremists pose to stability.
RFE/RL Radio Free Afghanistan correspondent Ayaz Khan says the charismatic Bhutto "was not only a liberal Pakistani politician but also a symbol of liberal politics in a region that's been increasingly haunted by extremism, terrorism, and fundamentalism."
He also says Bhutto's tough stance against militants echoed a prevalent view in Kabul that regards terrorist threats in both Pakistan and Afghanistan as inextricably linked.
Ayaz Khan notes that "just hours before her death she met with [Afghan President Hamid] Karzai to reiterate her support for the fight against extremism and terrorism that has afflicted the region and, more recently, the Pakistani government, the Pakistani street, and the Pakistani people."
The first of Bhutto's two terms as prime minister (1988-90 and 1993-96) came at a time when Pakistani intelligence was actively backing Islamic fundamentalists fighting to end the Soviet army's occupation of Afghanistan. Some of those fighters went on to form the Taliban movement that eventually provided an Afghan safe haven for Osama bin Laden and his Al-Qaeda terrorist organization.
Since her return to Pakistan nearly three months ago, the Radio Free Afghanistan correspondent says, Bhutto had "vowed to rid the country of the extremists responsible for the violence in Pakistan and Afghanistan," a position that made her a potentially valuable ally from Kabul's point of view.
Karzai Condemns 'Immense Brutality'
Her potential for helping to overcome tensions between Islamabad and Kabul was widely recognized. President Karzai had met with Bhutto just hours before she was killed. Karzai told a hastily arranged press briefing in Kabul after news of the killing that the perpetrators were "enemies" of Pakistan and of peace. "We in Afghanistan condemn this act of cowardice and immense brutality in the strongest possible terms," Radio Free Afghanistan quoted Karzai as saying.
Bhutto and Karzai at their meeting just hours before the explosion
Correspondent Ayaz Khan says Bhutto's shared view of the common terrorist threat -- along with her public statements of "wholehearted support for the internationally backed peace process in Afghanistan and what NATO and international forces had done" -- made her a possible uniter in dealings between Islamabad and Kabul, a position that he says ultimately "made her a prime target for terrorists."
Speaking to Radio Free Afghanistan hours after the assassination, Afghan Foreign Minister Rangin Dadfar Spanta said Bhutto "was so hopeful of winning the coming election, [and] of establishing a friendly relationship based on brotherhood with the Afghan nation and fighting against the common threat of terrorism."
Bhutto had received numerous death threats from Islamic militants. On the night of her return to Pakistan, as she paraded through the southern city of Karachi on October 18, a suicide bomber struck near her vehicle, killing 139 people. Bhutto was unhurt, but the dead included at least 50 of her security guards, who had formed a human chain around her vehicle to protect her.
At a news conference the following day, Bhutto said she would continue campaigning. She accused the authorities of failing to provide adequate security.