After Iraq invaded Kuwait in 1991, President George H.W. Bush did the improbable and convinced Syrian President Hafez Assad to join an American-led coalition against a fellow Baathist regime.

Today, these leaders' sons have another chance for a diplomatic breakthrough that could redefine the strategic landscape in the Middle East.

The recent announcement of peace negotiations between Israel and Syria through Turkey, and the agreement between the Lebanese factions in Qatar – both apparently without meaningful U.S. involvement – should serve as a wake-up call that our policy of nonengagement has isolated us more than the Syrians. These developments also help create new opportunities and increased leverage that we can only exploit through substantive dialogue with Syria.

Syria's leaders have always made cold calculations in the name of self-preservation, and history shows that intensive diplomacy can pay off. Secretary of State James Baker made more than a dozen trips to Syria before Operation Desert Storm, and remember President Assad's price: U.S. support for Syrian dialogue with Israel. The ultimate challenge – moving Syria away from its marriage of convenience with Iran – will certainly not happen overnight. But it's telling that Iran lobbied Syria not to negotiate with Israel and that Syria decided to proceed regardless.

To support Israel and isolate Iran, President George W. Bush should offer direct support for the Israeli-Syrian initiative. Promoting peace between our ally and its neighbors has always been a bipartisan cornerstone of our foreign policy. Syria views peace talks with Israel as part of a broader rapprochement with America, and its strong desire for U.S. involvement can work to our advantage. We know that high level, direct talks will require a sustained and credible American role, just as they did in 2000, when President Bill Clinton met repeatedly with Mr. Assad in bringing Syria and Israel to the brink of a deal. With so much at stake, it's in our interests to come to the table again.

The agreement by the Lebanese parties provides another opening. Syria must respect Lebanon's sovereignty and end its deadly meddling. But the fact that Syria's ally, Hezbollah, secured much of the political power it sought should remove Syria's excuse for failing to open an embassy, normalize relations, and finally demarcate the border with Lebanon. Hezbollah must eventually be disarmed, as United Nations Resolutions 1559 and 1701 require, but its agreement not to use force internally could be used to push Syria to shut off the supply of weapons.

Dialogue can open the door for greater cooperation on Iraq. Top Syrian officials have argued that Syria shares America's interest in a stable, secular Iraq and does not want a strongly pro-Iranian regime in Baghdad. Our partnership with Sunni tribes against al Qaeda may have further aligned our interests. As U.S. Ambassador to Iraq Ryan Crocker has noted, Islamic extremists also threaten Syria.

While Syria must crack down on the flow of foreign fighters into Iraq, Syrian President Bashar al-Assad claims positive steps have not been rewarded. We should test whether offering tangible benefits brings better results, starting with providing more humanitarian assistance for the nearly 1.5 million Iraqi refugees Syria has absorbed.

The U.N. tribunal investigating the murder of former Lebanese Prime Minister Rafik Hariri, which may soon issue indictments, is also creating pressure on the regime. If government officials are implicated, Syria could face increased international sanctions. The tribunal's pursuit of justice must never be a bargaining chip, but it adds an incentive to improve relations that we should capitalize on.

Tough economic times in Syria also create leverage. Although domestic oil production accounts for 60%-70% of the country's exports, Syria became a net oil importer in 2007. With a growing population, greater integration into the global economy and an easing of sanctions could be powerful incentives.

Make no mistake: Cooperation with Syria rests not on shared values, but on shared interests. Syria's pursuit of a suspected nuclear program underscores why any agreement must be verified. While many doubt Syria's intentions, we have real leverage and some inducements that have more value to Syria than cost to us. There is no guarantee of an agreement, but the potential payoff is huge, and our current policy is failing.

Israel's government has concluded that, rather than rewarding bad behavior, dialogue with Syria is the best hope for changing it. As Israeli Prime Minister Ehud Olmert said, "the chance overrides the risk, and with this hope I am going for a new path." We should do the same before the opportunity slips away.

Mr. Kerry, a Democrat, is a U.S. senator from Massachusetts. Mr. Hagel, a Republican, is a U.S. senator from Nebraska.