News that Reid praised Obama's electability as a "light-skinned" African American "with no Negro dialect, unless he wanted to have one" could weaken the political influence of the Nevada Democrat.
Reid is a key Obama ally who already faces a tough re-election battle in his home state.
Obama, who has accepted Reid's apology for the comment, needs a strong Harry Reid to help him pass health care legislation, a jobs bill, energy legislation and funding for the war in Afghanistan, among other legislative priorities.
"I accepted Harry's apology without question, because I've known him for years. I've seen the passionate leadership he's shown on issues of social justice, and I know what's in his heart," Obama said Sunday.
The president and other Democrats have signaled that the comment, which Reid made to authors Mark Halperin and John Heilemann in the midst of the 2008 presidential campaign, are no big deal.
"It definitely was in the context of recognizing in Sen. Obama a great candidate and future president," Virginia governor and Democratic National Committee chairman Tim Kaine said Sunday.
Some conservatives have also come to Reid's defense, including columnist George Will, who said on "This Week" Sunday that he didn't find a "scintilla of racism in what Harry Reid said."
But other Republicans said mild treatment of Reid's comment on race amounts to a Democratic double-standard.
"One of the things that makes the American people frustrated is when they see time and time again liberals excusing racism from other liberals," Liz Cheney said on "This Week."
Republican National Committee chairman Michael Steele called for Reid to resign, pointing out that then-Republican leader Trent Lott stepped down in 2002 after a fury ignited for his saying that his home state of Mississippi supported Strom Thurmond's 1948 segregationist run for the presidency
"If the rest of the country had followed our lead, we wouldn't have had all these problems over all these years, either," Lott said then at an event celebrating Thurmond's birthday.
Steele said Sunday, "If the standard is the one that we saw with Trent Lott as speaker -- as a leader at the time -- then I think this absolutely falls in that category."
Democrats argue, however, that an endorsement of segregation is entirely different from the intent of Reid's remark.
"I think that's a totally different context," Sen. Jack Reed, D-R.I., said.
In 2002, as a state senator, Obama said, "The Republican Party itself has to drive out Trent Lott. … They have to stand up and say this is not the person we want representing our party."
For their part, the authors of "Game Change" are trying to stay out of the fray, insisting revelations in the book should come as no surprise.
"We did over 300 interviews for the book, more than 200 people," John Heilemann said on "Good Morning America" today. "All were done on deep background. We did no off the record interviews. We have burned no sources in the book."
Mark Halperin said the book stands as it is, saying of the controversy, "What we've done is to try and write a book of history."