The American Israel Public Affairs Committee conference will feature keynote speeches by US President Barack Obama and Israeli Prime Minister Benjamin Netanyahu, who have just held one of the most discordant summits in recent history.
On Thursday, the US president for the first time publicly called on Israel to accept a return to territorial lines in place before the 1967 Arab-Israeli war, with mutual land swaps with Palestinians to frame a secure peace.
The next day, a somber-looking Netanyahu told Obama at the White House that Israel cannot go back to the 1967 lines "because these lines are indefensible" and warned him against chasing what he called a Middle East peace "based on illusions."
The exchange has sent new chills in relations between the two allies, with Israelis -- and their US supporters -- arguing that returning to the former border configuration would leave Israeli population centers vulnerable and mean uprooting hundreds of thousands of settlers from homes in the West Bank and east Jerusalem.
Yet while US lawmakers from all political stripes make an annual pilgrimage to AIPAC to pledge their support for Israel, it is the Arab world that is taking the spotlight in 2011.
In a short few months, the region including north Africa has been rocked by pro-democracy revolutions sweeping longstanding leaders from power in Tunisia and Israeli peace partner Egypt; civil war in Libya; deadly anti-regime unrest in Syria and Yemen; violent protests along Israel's border; and the killing by US forces of terror kingpin Osama bin Laden.
AIPAC is scrambling to grasp the magnitude of the changes sweeping the Middle East and assess exactly how they will affect Israel, its chance for peace and its all-important relationship with key ally the United States.
"It's a very different situation than in December... and dramatically so," a senior official in the pro-Israel lobbying community said this week.
A further development for AIPAC to digest when it convenes: the Palestinian Authority government of Mahmud Abbas has struck a high-stakes unity deal with Hamas, the rival Palestinian faction which Washington deems a terrorist group.
"The situation with Hamas has changed everything," the lobby community official said.
Yet broader developments abound, including revolt and unrest on Israel's doorstep.
"This is a tumultuous moment in the Middle East, with great hope and great promise, but also great uncertainty and perhaps great fear," Robert Satloff, who heads the Washington Institute for Near East Policy, told AFP.
Israel's relations with the Palestinians is an urgent issue, he said, but the conventional idea of a peace process in the midst of regional convulsion "doesn't seem to be relevant in the current moment."
What is top priority, according to Satloff, is that the democratic changes in the region "proceed well and end positively."
Also of increasing concern is Syria, whose embattled President Bashar al-Assad had also kept unrest to a minimum with Israel, but which the lobby official described as "this great unknown" now that Assad is facing mounting anti-regime protests and Washington has urged him to lead a transition.
"He's going, and we've got to deal with who comes next," the official said.
Marina Ottaway, director of the Middle East program at the Carnegie Endowment for International Peace, said the Arab Spring has been an "uncertain time" for AIPAC.
"They are not saying openly that they are against these transformations, but they are raising old issues," she said, particularly the fear that political transitions could be exploited by Islamic extremists.
And so AIPAC will use its significant clout on Capitol Hill to burnish the US-Israel relationship, and pressure lawmakers to pledge that they have Israel's back.
With senators and congressmen beating a path to AIPAC's meeting, Ottaway said it was clear the group held huge sway in Congress.
"The pro-Israel lobby is the only lobby that likes to play down its own importance," she said. "Usually, lobbyists do the opposite."