Over 15,000 pro-Israel US citizens are expected to attend the conference, as well as an estimated two-thirds of Congress and 3,600 students from over 630 campuses.
Clinton paints herself as the best candidate for Israel.
Democratic presidential frontrunner Hillary Clinton addressed AIPAC's annual policy conference in Washington DC, attacking Republican front runner Donald Trump for saying that he would be "neutral" on the Israeli-Palestinian issue.
"We need steady hands, not a president who says he's neutral on Sunday, pro-Israel on Monday and who knows what on Tuesday, because everything is negotiable. Well my friends, Israel's security is not negotiable," Clinton told the meeting of the US's largest Israel lobby.
"America can never be neutral when it comes to Israel's security or survival," she stated. "Anyone who doesn't understand that has no business being our president."
Clinton said that the turmoil of the Middle East poses great challenges to the US, but abandoning America's responsibilities in the region is not an option.
Clinton said that Iran's aggression, the rise of extremism and the growing effort to delegitimatize Israel on the world stage are converging to make the US-Israel alliance more necessary than ever.
"The US and Israel must be closer than ever, stronger than ever and more determined than ever to go against our common adversaries and advance our common values," she said.
Clinton said this was particularly so given the current wave of terror plaguing Israel. "These attacks must end immediately and Palestinian leaders need to stop inciting violence, celebrating terrorists as martyrs and stop paying rewards to their families."
She said that maintaining Israel's security was a strong national interest for the US.
"We must take our alliance to the next level and conclude a new ten year Memorandum of Understanding as soon as possible," Clinton said of current negotiations between Israel and Washington over a new military aid package for the Jewish state. This will send a clear message to Israel's enemies, she added, vowing to maintain Israel's qualitative military edge.
She called on the US to bolster Israel's missile defense and work together to create tunnel-detecting technology.
"One of the first things I'll do as president is invite the Israeli prime minister to visit the White House," Clinton said.
Clinton said that a negotiated two-state agreement remains the best way to ensure Israel's survival as a democratic and Jewish state. "Inaction cannot be an option," she stated.
"As president I would continue the pursuit of direct negotiations," she said, adding emphatically that she would oppose a UN Security Council resolution to impose a solution from the outside.
Republican presidential candidates Sen. Ted Cruz, Donald Trump and Ohio Gov. John Kasich were set to address the AIPAC conference later on Monday. House Speaker Paul Ryan will also address the confab on Monday.
On Sunday, Vice President Joseph Biden offered a forceful defense of Israel's security posture at AIPAC, delivering what is likely his last speech to the group after a 30-year career in public service drew him close to the pro-Israel organization.