It was a brazen and sophisticated attack launched against the Syrian regime. The explosion happened in the Syrian capital as Cabinet ministers and other senior officials met at the national security building.
The defense minister is the most senior government official to be killed in the Syrian civil war as rebels battle to oust Assad. Assad's brother-in-law was among the most feared in Assad's inner circle.
Initial reports said a suicide bomber caused the blast, but a rebel commander said his forces planted the bomb inside the room where the officials were meeting.
Defense Secretary Leon Panetta said the bombing shows that the country's crisis is "rapidly spinning out of control." He said that is all the more reason for the international community to bring "maximum pressure" on Assad to step down and permit a stable transfer of power.
In a bid to turn up the heat, the Obama administration slapped financial sanctions on many top members in Syrian President Bashar Assad's government, targeting the prime minister and 28 other cabinet ministers and senior officials. The Treasury Department announced the sanctions just hours after the bombing.
"Today's actions reflect the unwavering commitment of the United States to pressure the Assad regime to end the carnage and relinquish power," said David S. Cohen, the undersecretary for terrorism and financial intelligence at Treasury. "As long as Assad stays in power, the bloodshed and instability in Syria will only mount."
The violence in Syria has been raging for months. Activists say more than 17,000 people have died since March 2011.
British Defense Minister Philip Hammond suggested that Russia and China hold the key to finding a peaceful solution.
"The regime exists at the moment because it receives tacit support from other powers in the world," he said. "If those powers are sending clear messages about the limits of their tolerance for the activities of the regime, that will be an effective constraint on the activities of the regime."