NEW YORK - Every Manhattanite dreads this week.

Motorcades block the streets and presidential suites at the city's swankiest hotels are booked solid. By the looks of it, NYPD occupies every street corner around the U.N.'s East River location, diplomatic security fills in the gaps and government aides travel in swarms.

The 69th United Nations General Assembly kicks off this week and given the state of our planet, a meeting of the world's leaders comes not a moment too soon.

"The world is facing multiple crises," U.N. Secretary General Ban Ki-moon told reporters.

"Each has its own dynamics, and requires its own approach. But all have featured atrocious attacks on civilians, including children. All have dangerous sectarian, ethnic or tribal dimensions. And many have seen sharp divisions within the international community itself over the response."

A chaotic week awaits and with the U.S. ramping up its campaign against ISIS, the world's largest Ebola outbreak in history spreading, and the war between Ukraine and Russia unflinching, here's what you need to know about U.N. week.

1. On The Agenda:

Syria was at the top of last year's agenda and this year, it's all about ISIS. The growing threat of the Sunni Islamic State group will dominate the floor during the general debate. And behind closed doors President Obama hopes to recruit more allies to join the roster of the U.S.-led coalition. For the first time since 2009, Obama will chair a session on ISIS Wednesday afternoon, urging the Security Council to pass a resolution aimed at cracking down on foreign fighters headed for Syria and Iraq.

"Together, we will address the horrendous violence in Syria and Iraq, where conflict and governance failures have provided a breeding ground for extremist groups," said the secretary general. "I welcome the growing international consensus to act against this serious threat to global and regional peace and security," he added.

Following Sunday's massive People's Climate March through the streets of New York, some 140 leaders will take part in Tuesday's Climate Summit, gearing up for another global discussion in Paris next year.

Even the Secretary General hit the streets on Sunday, along with an estimated 400,000 activists, according to the event's organizers.

The Ebola outbreak has now killed more than 2,700 people according to the World Health Organization. With nearly 5,762 cases across five West African nations, it is the largest Ebola outbreak in history.

The problem demands a global response. America's U.N. Ambassador Samantha Power said last week, "the United Nations was built for global challenges like this."

The director-general of the WHO, Dr. Margaret Chan, described the outbreak as "the greatest peacetime challenge that the United Nations and its agencies have ever faced."

High level meetings are slated for Thursday, just a week after the Security Council declared Ebola a "threat to international peace and security."

2. The No Shows:

Syrian President Bashar al-Assad will skip this year (again!) and the country's permanent representative to the U.N., Bashar Ja'afari will keep the seat warm. As the three and a half year Syrian civil war rages, the head of the U.N. commission told the U.N. Human Rights Council in Geneva last week "the Syrian government remains responsible for the majority of the civilian casualties, killing and maiming scores of civilians daily."

But newcomer Hadi al-Bahra, the president of the Syrian Opposition Coalition, is in town and spoke with ABC News' Bob Woodruff on Sunday.

On peace in Syria, al-Bahra told Woodruff on This Week, "If it's done correctly, it could be done within two to three years at max."

Though invited, Russian President Putin is blowing off the whole affair. As a member of the U.N. Security Council, Foreign Minister Sergei Lavrov will vote this week on behalf of the Kremlin.

And for the first time in 15 years, North Korea is sending a foreign minister, Ri Su-yong, reports South Korean daily Joongang Daily . According to the paper. This is only the third time the country has sent a representative since the Hermit Kingdom joined the United Nations.

3. The Rookies

A few notable rookies will make their debut at the General Assembly, including Ukraine's new President Petro Poroshenko and Indian Prime Minister Narendra Modi. This is Modi's first trip stateside after he was denied a visa back in 2005 for his failure to stop violent religious riots in 2002.

Former military strongman, Egyptian President Abdel Fattah el-Sissi, will represent his country for the first time since taking office in June. Ahead of his visit, el-Sissi told the Associated Press: "We are completely committed to giving support" to the fight against ISIS. "We will do whatever is required."

The world's newest head of state, Afghanistan's President-elect Ashraf Ghani, will be watching from Kabul this year. After two rounds of voting and months of diplomatic wrangling, Ghani's victory was announced last weekend and he is expected to be sworn in early next week.

4. Awkward Encounters

It's that time again when the Iranian head of state and the American president are within feet of each other. For most of the year, more than 6,000 miles separate President Rouhani and President Obama, but this week the two leaders will both attend the General Assembly. Last year rumors swirled about a possible handshake that culminated with a quick phone call as Rouhani drove to JFK airport.

And while the two leaders are not expected to meet at the U.N., Secretary of State Kerry and Iranian Foreign Minister Zarif met for more than an hour on Sunday. Kerry noted that "this week is an opportunity to make additional progress" and stressed that "it is our intention to do so." A State Department official said "going forward, the Secretary and Foreign Minister Zarif agreed to meet further as needed while in New York this week."