FORTUNE — The glasses of Sauvignon Blanc being passed about wasn’t what was fueling the buzz that filled the U.S. State Department’s Jefferson Room Monday evening. Instead, it was the knowledge that the “strongest advocate for women in the world,” as assistant secretary of state Ann Stock put it, was about to enter the room.
Secretary of State Hillary Clinton addressed attendees of the Fortune Most Powerful Women dinner in Washington, launching the seventh annual Fortune/U.S. State Department Global Women’s Mentoring Partnership. Unable to stay for the entire event, Clinton joked with the crowd, “We worked out a date for the prime minister of Japan to come to Washington and when the White House said, ‘Well, why don’t you have a dinner for him at the State Department?’ I said, ‘Well, we’ve already got this other dinner at the State Department, and I’m not about to ask them to move.’” Instead, she asked Japanese Prime Minister Yoshihiko Noda to head to the National Geographic Society building just a mile or so away (the dinner she had to run to).
The mentoring program connects rising businesswomen from emerging economies with U.S. corporate superstars. Over the next month, the 25 mentees – from 17 different countries – will connect with women like Tory Burch, Molly Ashby of Solera Capital, Susan Chambers of Wal-Mart (WMT), Marissa Mayer of Google (GOOG), Bridget Van Kralingen of IBM (IBM), and Time Inc. CEO Laura Lang (Time Inc. is Fortune’s parent company). “I really believe in this kind of mentoring and networking, because all too often it’s lonely out there, it’s hard out there, and you need support and guidance along the way,” Clinton told the crowd. “And for me, that’s not only important on a personal level, but I’ve seen the difference that women leaders, women activists, women citizens can make from one end of the world to the other.”
Clinton then opened the floor for Senator Barbara Mikulski (D-Md.), the longest-serving female in Congress. After making a joke about the now infamous picture of Clinton sipping on a beer in Cartagena (“It’s hard to drink the water, and the beers are pasteurized and safe.”), Mikulski shared a true nugget of advice with the mentees: You’ll face hardship, you’ll face ridicule, people will say no. But you’re greatest no may lead to your greatest yes.
Fortune senior editor-at-large Nina Easton interviewed Samantha Power. As chair of the White House’s newly created Atrocities Prevention Board, she described the events unfolding in Syria. The only thing worse than reading about them from the outside, she said, is when you’re reading about them from the inside. “You don’t snap your fingers and change human nature,” Power noted, but the board is focused on addressing the issues, working with foreign states, and asking, “What else should we be doing?” The 36-week pregnant Power has a can-do attitude. Her advice for other young women figuring it all out? Channel your passion and “know something about something.” Develop a mastery, she said, and that will be what distinguishes you in a crowd.
Easton returned to the stage later in the evening with Anita Dunn, managing director of SKDKnickerbocker, and Susan Molinari, vice president of public policy and government affairs at Google. The growing tension between Republicans and Democrats is on account of gerrymandering, both women argued, but also because politicians from opposite sides of the aisle don’t socialize with one another enough. “There’s far less political incentive to cross the political aisle,” Dunn said. “Conservatives and liberals get thrown out [of office] for cooperating with one another.”
As for the lack of women on Capitol Hill? “Part of it is undeniably the rough ride,” Molinari offered. “You have to have skin that’s so thick [to survive] no matter what they accuse you of.”
The former congresswoman also cited the pain that running for office can cause a family. When everything’s fair game, she said, your kids may read some awful things about you online. Dunn agreed, asking the crowd, “Who here wants to step up?” She was met with little enthusiasm, but believes the next generation of women will be more interested in becoming politicians. Thanks to Title IX, Dunn said, the next generation isn’t scared to compete. With self-confidence, leadership, and teamwork skills, they’ll be ready to run.
Keeping with Dunn’s optimism, Molinari ended the night by addressing the mentees and powerful women in the room: “You have been given more than 99% of your sisters… Now do something with it.”