BBC News, Washington
Benjamin Netanyahu and Barack Obama have already had one good meeting, last summer, but they were not in power yet.
Now that they are prime minister and president, they will have to get down to business and there are concerns about a clash between the two leaders who do not see eye to eye on key issues.
The last time Mr Netanyahu was in Washington as Israel's prime minister was almost 10 years ago and two key factors mean he will be dealing with a very different dynamic when it comes to peace talks.
Iran's nuclear programme and regional ambitions will be topping the agenda.
Ten years ago, the issue was not really on anyone's radar.
Now it is a major concern for the US and Israel, and even some Arab countries.
Israel is worried about the Obama administration's diplomatic overtures to Tehran and Mr Netanyahu will want reassurance from Washington and may seek to tie starting talks with the Palestinians to concrete signs that Iran is being kept in check.
But the sequencing will be key.
On his way to Washington, Uzi Arad, Mr Netanyahu's national security advisor, seemed to signal Israel's patience on Iran was running thin.
However, Mr Netanyahu will also have to contend with a new, popular American leader who made Palestinian statehood and peace in the Middle East one of his top foreign policy priorities, right from the start.
Mr Obama appointed a special envoy to the region, retired Senator George Mitchell, who is credited with sealing the Good Friday peace deal in Northern Ireland.
The US president is also hoping he can count on support at home for this difficult mission.
"The American public supports a two-state solution, supports America driving that process forward and increasingly understands this will require tough love for both sides, certainly with the Israeli ally," said Daniel Levy, a former Israeli negotiator now with the Washington liberal think tank, New America Foundation.
"Interestingly what we also see, what is also being expressed now is that this applies to the Jewish community. Barack Obama got 78% of the American Jewish vote and polling shows the support has remained solid," Mr Levy adds.
During Mr Obama's visit to Israel last summer, he banked some political capital: meeting Israeli leaders, showing support and sympathy for America's top ally.
He also made strong statements in support of Israel at last year's conference of the American Israel Public Affairs Committee (AIPAC). So at this year's gathering of the pro-Israel lobby, there was already some of that tough love.
"Israel has to work towards a two-state solution," said Vice-President Joseph Biden.
"You're not going to like my saying this, but not build more settlements, dismantle existing outposts, and allow the Palestinians freedom of movement based on their first actions. This is a "show me" deal, not based on faith, show me."
In return Israel will want reassurances from Washington about containing Iran and its growing regional ambitions.
But Hillary Clinton last month warned Israel that the Obama administration will not agree to handling with Iran first before addressing the issue of Palestinian statehood - the two issues will have to be dealt with in parallel.
"For Israel to get the kind of strong support it is looking for vis-a-vis Iran, it cannot stay on the sidelines with respect to the Palestinians and the peace efforts. They go hand in hand," she said during a testimony in Congress on 23 April.
Though the circumstances have changed, Mr Netanyahu's done this all before and he has proved a tough, sometimes frustrating partner.
Many officials in the Obama administration are former members of the Clinton administration and will remember the Israeli leader from those days.
American leaders are reluctant to pressure Israel into peace and have faced a lot of heat whenever they did, whether Jimmy Carter, Ronald Reagan or George H W Bush who in 1991 tried to block loan guarantees for Israel and tied them to Israel freezing settlement activity on occupied Palestinian territory.
"If you want to take on Israel, you have to prepared to take the heat, it can get awfully intense," said Richard Haass, who was a senior advisor to Bush Senior from 1989 until 1991 and is now president of the Council on Foreign Relations."
"But today the pressure would probably not be what people often think about, things like aid and so on, Israel's economy is too large, the US is not going to do anything that would endanger Israel's security," he says.
"The real pressure would probably come in the way of words. Israel is a democracy, what the US says echoes around," Mr Haass says.
But at the meeting on Monday, it will still be about smiles and handshakes and a showdown is unlikely, even if there might be some tension.
The three-hour-long talks including a lunch will, however, set the tone for the weeks to come.
President Obama is expecting to meet the Palestinian and Egyptian leader next week and he will give a speech to the Muslim world in Cairo next month.
His talks with Mr Netanyahu will help him determine what he can expect from the Israel, how much progress he might be able to make in the Middle East and how fast.