Yet the war on drugs that has drawn some of the sharpest distinctions among leaders at the two-day gathering.
On Saturday, leaders debated how to address drug trafficking and violence in the hemisphere, with several calling for new approaches -- something U.S. President Barack Obama said he was open to, though he closed the door on legalization.
Colombian President Juan Manuel Santos compared continuing the existing policies to address this issue to being on "a stationary bike" -- making little progress, despite ample effort.
"I think the time has come to simply analyze if what we are doing is the best we could be doing, or if we can find an alternative that would be more effective and less costly to society," he said. "This is a topic of extreme political sensitivity."
Santos added, "One extreme can be to put all users in prison. On the other extreme, legalization. In the middle there may be more practical policies, such as decriminalizing consumption but putting all the efforts into interdiction."
The possibility of drug legalization has gained traction in Central America, which is being squeezed between suppliers to the south and consumers to the north.
Yet the idea goes against decades of the prohibitionist policy backed by the United States, which is largely followed and enforced in Latin America and the Caribbean.
Obama voiced his view that legalizing drugs isn't a valid option in the United States twice on Saturday -- first during a meeting of business leaders alongside Brazilian President Dilma Rousseff and Colombian President Juan Manuel Santos and later during the hemispheric event's opening day session.
"I think it is entirely legitimate to have a conversation about whether the laws in place are doing more harm than good in certain places," he said at the meeting of business leaders. "I personally, and my administration's position is, that legalization is not the answer."
He reiterated that position while talking at the summit itself, saying "the United States will not be going in this direction."
Nations in the Americas -- including the United States -- have "mutual responsibilities" to tackle the issue, Obama said. To that end, he announced an increase to more than $130 million of funds dedicating to bolstering security and going after narco-traffickers and "gangs" in the region.
In addition to the drug issue, a major talking point in the run-up to the summit was on leaders from the hemisphere who are not present in the coastal city of Cartagena, Colombia.
Venezuela's foreign minister told reporters Saturday that Venezuelan President Hugo Chavez will not attend because of health reasons. Chavez had recently returned to his country from Cuba, where he underwent cancer treatment.
Cuba, which is not a member of the Organization of American States, was not invited to join the leaders. But there was a last-minute push by Ecuador's leftist President Rafael Correa to get Cuban leader Raul Castro a seat at the table.
Correa boycotted the summit because of Cuba's exclusion.
Santos, a key U.S. ally, said in his opening remarks Saturday that it was time to overcome such issues -- calling it unthinkable if Cuba is not part of the next Summit of the Americas, as well as nearby Haiti.
At the business leaders' meeting, Rousseff spoke of a need for a "virtuous relationship" based on respect and equality among economies, while Santos said he welcomed a "change of mentality in relations between north and south."
Obama pointed out one change he'd like to see: "I think in Latin America, part of the change in mentality, is also not always looking at the United States as the reason for everything ... that goes wrong."
There are many examples of increased cooperation between the United States and Latin America, but they are not always flashy and don't draw the same type of attention that conflicts do, Obama said.
"Oftentimes in the press, the attention at summits like this ends up focusing on the controversies," the president added. "Sometimes those controversies date back to before I was born."
In his speech later Saturday, the U.S. president stressed that there are "no senior or junior partners, (but) simply partners" in the region.
"No other region so profoundly affects the daily lives of people in the United States, including the tens of millions of Hispanic Americans who bind our families," Obama said, according to his prepared remarks. "I firmly believe that this region is only going to become more important to our future."
He played up the economic ties -- touting earlier a 46% increase in trade between the United States and Latin American and Caribbean countries. Two initiatives, including a inter-continental small business network and broadband expansion effort, were announced by the United States in recent days to further bolster relations and the region.
Obama ended his speech on an optimistic note, highlighting progress that's been made and predicting the future can be even brighter with cooperation and coordination.
"Between us, we represent nearly one billion people. They ask nothing more than that we come together and make the progress that none of us can achieve alone," he said. "We can go further together. That's why we're here."
The summit's start was momentarily overshadowed by two security incidents -- one involving bomb blasts and another involving Secret Service in Colombia to protect the U.S. delegation.
Some 11 Secret Service agents and officers are being investigated over preliminary findings that they allegedly brought back several prostitutes to a hotel in Cartagena, U.S. government sources familiar the investigation told CNN.
The Secret Service personnel have since been sent back to the United States and put on administrative leave, the agency said. The U.S. military said that five U.S. troops who were working with the Secret Service on this assignment are also under investigation for missing curfew and alleged "misconduct" at the same Colombian hotel.
Separately, two small blasts occurred nearly back-to-back Friday in Cartagena.
The explosions -- one near a bus station and another near a shopping mall -- occurred a good distance away from where world leaders were gathering, said Alberto Cantihho Toncell, a spokesman for the Colombia National Police.
There were no casualties, and only minor damage was reported, Toncell said.
The explosions came on the heels of a similar one earlier in the day near the U.S. Embassy in the capital city of Bogota, authorities said.