Among the speakers at the conference, which opens on Sunday, will be Dick Cheney, the US vice-president, Nancy Pelosi, the house speaker, and Tzipi Livni, Israel's foreign minister.
The organisation was set up shortly after Israel's foundation in 1948 and now has 100,000 members.
It is credited with winning billions of dollars in US aid for Israel, including for buying the latest military weaponry.
Nathan Guttman, Washington bureau chief for the US-Jewish newspaper, The Forward, says: "Aipac is very influential because they have grass-roots organisation. When a congressman first comes to Washington, he already knows Aipac, he has met their activists in his district, he knows what it means to be pro-Israel."
Although Aipac does not make direct campaign contributions, it has spent millions of dollars on professional lobbyists and paying for politicians to visit Israel.
In the past two election cycles, pro-Israel groups have given more than $9m to congressional candidates, with slightly more than half going to Democrats.
'Most powerful lobby'
Certainly, if you are ranking Americans involved in pursuing a foreign government or country's interests, Israel outranks them all.
Massie Ritsch is an analyst for the Centre for Responsive Government, a lobbying watchdog group.
Ritsch said: "The pro-Israel lobby is the most powerful among foreign interests that want contact with the federal government.
"Members of congress have travelled to Israel more often in the past two years, more often than they have been to Chicago, in our own country [the US].
"It is the most travelled foreign destination for members of congress."
Delegates say Iran will be the number one issue at this year's Aipac conference.
Guttman said: "We will hear a lot about the danger of a nuclear Iran ... thousands of Aipac supporters will go to the [Capitol] Hill on Tuesday and lobby to toughen sanctions against Iran."
In the US, the power of the pro-Israel lobby is a sensitive topic.
When a pair of university professors, Stephen Walt and John Mearsheimer, published a paper last year suggesting the pro-Israel lobby's power distorted American foreign policy, they were attacked and labelled anti-Semites.