Infiltration of the rebels forces by extremist groups like Jabhat al-Nusra and al Qaeda in Iraq "is always going to be a factor" for however long Washington decides to funnel weapons into Syria, Hagel told reporters at the Pentagon.
"The [Syrian] opposition has many different groups" within its ranks, according to Hagel. The Department of Defense "will have to be assured" American arms do not find their way into Jabhat al-Nusra or al Qaeda arsenals.
Hagel declined to comment on recent reports claiming shipments of American weapons could arrive in Syria within the next two weeks.
Gen. Salim Idris, the top commander of the Free Syrian Army, said earlier this month that his forces had recently obtained the weapons but refused to say who supplied the arms.
The Free Syrian Army is the largest and most organized of the rebel factions fighting for Assad's ouster.
President Obama ordered the CIA to begin setting up distribution points in neighboring Jordan and Turkey to start providing American arms to Syria's rebels.
While the Syrian arms operation will be run by the CIA, U.S. military leaders will be monitoring the program, to ensure the weapons get to the correct forces inside the country.
"The opposition represents many different groups. And we will always be and have to be assured that assistance we give to the Syrian [rebels] gets to the right people," Hagel said.
"That isn't a decision that can be answered quickly. It's a constant process of assessment," he added.
The White House's decision to arm the rebels came after U.S. intelligence officials concluded the Assad regime had used chemical weapons against opposition forces.
Assad's use of those weapons crossed a "red line" with the Obama administration, prompting the president to approve the arms supplies to Syria's rebels.
Prior to the intelligence report, the DOD had been opposed to arming opposition forces over concerns of terror groups gaining access to those weapons.
On Monday, Syrian Foreign Minister Walid al-Moallem warned Washington that the weapons supplies would only lead to more bloodshed in the country and prolong the three-year civil war.
Arming the rebels "is a dangerous decision because it aims at prolonging the crisis, prolonging the violence and killing and encouraging terrorism," he told reporters in Turkey.