Klain joined the Clinton-Gore campaign in 1992 and was involved in both of Bill Clinton's presidential campaigns. He oversaw Clinton's judicial nominations. In the White House, Klain was Associate Counsel to the President, directing judicial selection efforts and leading the team that won confirmation of Supreme Court Justice Ruth Bader Ginsburg. In 1994, he became Chief of Staff and Counselor to Attorney General Janet Reno and in 1995, Chief of Staff to Al Gore.
Gore campaign 1999–2000
During Klain's tenure as Gore's Chief of Staff, he was seen as too loyal to Clinton by some longtime Gore advisors. In 1999, feuding broke out between Clinton and Gore loyalists. Klain was ousted by Gore campaign chairman Tony Coelho in August 1999.
In October 1999, Klain joined the Washington, D.C. office of O'Melveny & Myers, a law firm. In 2000, Klain returned to the Gore campaign, which named him General Counsel of Gore's Recount Committee.
During the 2004 presidential campaign early primaries, Klain worked as an adviser to Wesley Clark during Clark's run for president. In the general election, Klain was heavily involved behind the scenes in John Kerry's campaign.
Klain served as an informal adviser to Evan Bayh who is from Klain's home state of Indiana. In 2005, Klain left his partnership at O'Melveny & Myers to become Executive Vice President and General Counsel of Revolution LLC, a technology venture capital firm launched by AOL co-founder Steve Case. At the time of his October 2014 appointment as Ebola response coordinator, he was General Counsel at Revolution LLC and President of Case Holdings.
Obama administration 2008–2015
Klain briefing President Obama in his role as Ebola Response Coordinator
Klain was mentioned as a possible replacement for White House Chief of Staff Rahm Emanuel, but opted to leave the White House for a position in the private sector in January 2011.
In 2011, amid concerns about whether the now-defunct solar-panel company Solyndra was viable, Klain approved an Obama visit, stating, "The reality is that if POTUS visited 10 such places over the next 10 months, probably a few will be belly-up by election day 2012."
On October 17, 2014, Klain was appointed the "Ebola response coordinator" sometimes referred to as Ebola "czar." Although Klain, according to Julie Hirschfeld Davis writing in The New York Times, had "no record or expertise in Ebola specifically or public health in general," the choice was praised by Ezra Klein for his bureaucratic experience with coordinating agencies. His term as Ebola response coordinator ended in February 2015.
Since leaving the Obama administration, Klain has worked as an external adviser to the Skoll Foundation Global Threats Fund and is Executive Vice President and General Counsel at the investment firm Revolution LLC.
Klain is married to Monica Medina, a lawyer and environmental activist who served as Principal Deputy Undersecretary of Commerce for Oceans and Atmosphere and is currently at the Walton Family Foundation. They have three children, Hannah, Michael, and Daniel.