Following the opening session, Clinton, Netanyahu and Abbas will continue to hold a private meeting. It is expected that Netanyahu and Abbas will hold further talks later this month in Egypt.
Since he took office, U.S. President Barack Obama has made the Middle East peace process one of his top diplomatic priorities and spared no effort to bring Israelis and Palestinians back to the negotiation table.
Despite their small sizes, Israel and Palestinian areas have important implication on U.S. overall strategy in the region. President Obama and Secretary Hillary Clinton have both said solving the conflict between the two sides concerns the national interests of the U.S..
Analysts believed that Israeli-Palestinian conflict has important implications on strategic issues, including Middle East oil supply, U.S. image in the Muslim world and U.S. isolation effort on Iran.
On Wednesday, after holding bilateral meetings with the four other leaders involved in the Middle East peace process, Obama said that the United States is ready to seek a lasting peace between the Israelis and Palestinians.
However, the peace talks, since it first started in 1993, have always been in the haunting cycle of "hope-to-collapse."
The issue of settlement construction has posed an immediate challenge to the direct talks, with Netanyahu on Tuesday saying he would not extend a moratorium that expires on Sept. 26.
Incitement from both sides, such as the killing of four Israelis on Tuesday by a gunman near the West Bank city of Hebron, could also derail the fragile peace process.