Sebelius, 60, a two-term governor and a former state insurance commissioner, has had successes working across party lines in Topeka, but her effort to raise taxes on tobacco to fund a modest expansion of government health benefits has encountered resistance from lawmakers.
"She is a Democratic governor from a Republican state. She had to be pretty competent to survive that. But health care was a disappointing exercise," Edmund F. Haislmaier, a senior research fellow in health policy studies at the Heritage Foundation, told the Washington Post. "This is kind of an outline of what you are going to see play out nationally. People on both sides want the same goal, but they go at it differently."
When she ran for re-election in 2006, Sebelius named a Republican, Mark Parkinson, as her lieutenant governor. Sebelius won re-election that year with 58 percent of the vote in a state where registered Republicans outnumber Democrats by more than 300,000.
As insurance commissioner, Sebelius also helped block the sale of the state's Blue Cross/Blue Shield insurance program to a for-profit health care group because of concerns it would have raised rates.
On Monday, Mr. Obama introduced Sebelius and Nancy-Ann DeParle, a health policy figure during the Clinton administration, to head the White House Office for Health Reform.
"There's no easy formula for fixing our health care system," President Obama said. But he added: "I didn't come to Washington to take the easy route ... I came here to work for the American people. I came here to deliver the sweeping change the people demanded when they went to the polls in November."
The announcements came just days before Mr. Obama holds a White House summit on health care. Lawmakers from both parties and representatives of major interest groups, from insurers to drug companies to consumers, will attend.
An early supporter of Mr. Obama's campaign for the White House, Sebelius was rumored to be on the short list of candidates for vice president before Joe Biden was named to the post.
Mr. Obama's first pick to head the health agency, former Senate Majority Leader Tom Daschle, withdrew his name from consideration last month after controversy emerged over his tax payment record.
Capitol Hill veteran Daschle was expected to be a savvy guide for Mr. Obama's health care reform efforts in Congress. While her credentials are strong, Sebelius may need more time to build a working relationship with Congressional power players.
"It signals that Sebelius will be one of many voices in the administration on health care - rather than the chief figure as Tom Daschle would have been - and the effort will be run out of the White House," Politico reported.
If confirmed, Sebelieus will head up agency responsible for everything from Medicare to food safety to the National Institutes of Health.
Obama made his opening move on health care reform last week: his speech to a joint session of Congress and a budget that set aside $634 billion over 10 years as a down payment on coverage for all.