Created in 2001, the foundation has allowed the ex-president to tackle problems across continents and burnish his legacy. It now serves as a home base for Hillary Rodham Clinton as she considers whether to run for president in 2016. And it also could become a launching pad for the couple's only child, 33-year-old Chelsea Clinton, should she eventually become a political player in her own right.
"It's a good thing to make big bets in philanthropy," the former president declared at the annual meeting, introducing a short video on the foundation's work narrated by actor Morgan Freeman. "What began with one man's drive to help people everywhere," Freeman said, "moved quickly into a foundation full people of great passion and great gifts."
The four-day CGI meetings, an initiative of the foundation held every year since 2005, offered a study in how the Clintons have transitioned from the White House to create a global clearinghouse to address big problems like AIDS prevention, nutrition, women's equality and poverty.
In a testament to the Clintons' ability to convene big names, the ballroom was awash with former Clinton administration officials, CEOs and corporate executives, and celebrities.
As the ex-president searched for his notes backstage, U2 frontman Bono kept the crowd entertained with an impromptu Clinton impression, complete with a Southern drawl. In smaller sessions, actor Sean Penn talked about his development work in Haiti and actress Kate Hudson promoted leadership roles by women.
The former first lady and New York senator said she would lead an effort through the foundation to evaluate the progress made by women around the globe in advance of the 20th anniversary of her remarks at a U.N. women's conference in Beijing. As first lady, Clinton famously declared at the 1995 conference that "human rights are women's rights and women's rights are human rights, once and for all."
During a session on Wednesday, Mrs. Clinton announced three new commitments to help women around the globe, including a $1.5 billion effort over the next five years to help businesses owned by women. Financial partners include Coca-Cola, Wal-Mart and Exxon Mobil.
"This is such a perfect example of CGI networking," she said. "Leveraging social capital and real capital — it's a great combination."
It's that very combination of money and philanthropy that could serve as a line of attack against the former secretary of state if she seeks the White House. The family has been raising money to build the foundation's endowment, holding recent fundraisers in New York's Hamptons and Washington. A benefit concert in London is planned for this fall, along with events in Washington and Miami.
Bill Clinton was forced to defend his foundation in August after media reports of infighting among staff and questions over the organization's financial management. The foundation disclosed that an outside firm conducted an audit in 2011 that recommended a stronger management staff and a more independent board.
Earlier this week, the former president said he was grateful for the work of his former aide, Douglas Band, after a lengthy report in the New Republic described an overlap between Band's business clients and donors to the foundation.
Republicans have signaled that the foundation's work would be fair game if Mrs. Clinton runs for president in three years. Kirsten Kukowski, a spokeswoman for the Republican National Committee, cited "mismanagement and conflicts of interest" within the foundation and said it showed "how the Clintons operate and is part of the baggage tied to Hillary."
Democrats call it just another attack du jour against the Clintons and say the charitable work speaks for itself. The foundation said this week that it had helped more than 5 million people with AIDS access medication in 70 countries, its agriculture work in Africa had helped 4,300 farmers feed 30,000 people, and its work led to the planting of 4.5 million trees in Rwanda and Malawi.
"Everything and anything will be used against them, but if that's the biggest complaint, that her family has helped save lives around the world, to quote a past president, 'Bring it on,'" said Paul Begala, a former Clinton White House adviser.
The foundation's future could rest in the hands of Chelsea Clinton, who has traveled extensively on its behalf and serves as vice chair. The former first daughter presided over a panel on noncommunicable diseases and announced several philanthropic commitments this week, including efforts to provide clean drinking water and promote the health of women and children in Latin America.
The youngest Clinton has hinted that politics could be in her future. In an interview with CNN from Rwanda last month, she said she was "attempting to lead a purposely public life" and that she might consider politics if she thought she could make a difference.