"Pakistan must demonstrate its commitment to rooting out al Qaeda and the violent extremists within its borders," he said. "And we will insist that action be taken -- one way or another -- when we have intelligence about high-level terrorist targets."
Holbrooke, who will take a leadership role in many of these meetings, returned recently from a donor conference where he secured $5.5 billion in pledged aid for Pakistan, including $1 billion from Japan and $330 million from Iran.
Other issues will be addressed in these two-day trilateral talks as well, including corruption, border posts, water management, food security, job creation, trade ties, building police forces, preparing relief efforts for the future refugees who may soon be displaced as the United States intensifies military operations, and addressing their problems with a "whole of government" approach so matters aren't just handled militarily.
Today's and Thursday's meetings won't just bring the three presidents together.
The intelligence chiefs from both countries will meet with CIA director Leon Panetta at Langley; the ministers of interior will meet with Attorney General Eric Holder and FBI director Robert Mueller; the finance ministers will meet with Deputy Secretary of State Jack Lew and the agriculture ministers will meet with Agriculture Secretary Tom Vilsack.
In many cases, the Afghan and Pakistani officials have not met their counterparts from across the border, so these talks will be new for them.
"Success in one country leads to success in another," a senior administration official said.
ABC News' Huma Khan, Kirit Radia and Luis Martinez contributed to this report.