Independents helped Obama and the Democrats win the White House and Congress in 2008. Retaining their votes is vital to any Democratic strategy.
"What happened is that independents, the very people who put together the winning coalition for Barack Obama and Democrats and put them in power, are fleeing in droves," said Sen. John Cornyn, R-Texas, chairman of the National Republican Campaign Committee.
The Democratic leadership took losing the historically liberal seat in an historically liberal state to heart, pledging to take seriously the message voters were sending.
In a message to voters, Sen. Robert Menendez, D-N.J., the chairman of the Democratic Senate Campaign Committee, said the party would better respond to voters fears about the economy.
"I have no interest in sugarcoating what happened in Massachusetts," Menendez said. "There is a lot of anxiety in the country right now. Americans are understandably impatient. The truth is Democrats understand the economic anger voters feel. That's in large part why we did well in 2006 and 2008.
"In the days ahead, we will sort through the lessons of Massachusetts: the need to redouble our efforts on the economy, the need to show that our commitment to real change is as powerful as it was in 2008, and the reality that we cannot take a single thing for granted and cannot afford even a second of complacency."
Brown beat Coakley with 52 percent of votes to her 47 percent.
Though they can no longer thwart a Republican filibuster, Democrats maintain the largest Senate majority either party has enjoyed since 1979 and still have the ability to pass legislation through reconciliation, a process that bypasses normal Senate rules by requiring only 51 votes.
While many Democrats insist the Massachusetts race was not a referendum on President Obama or a preview of what is to come in November, Republicans are trumpeting their victory.
"As we look forward to the mid-term elections this November, Democrats nationwide should be on notice: Americans are ready to hold the party in power accountable for their irresponsible spending and out-of-touch agenda, and they're ready for real change in Washington," said Cornyn.
In a new ABC News/Washington Post poll, only 35 percent of the American people said President Obama has done enough to improve the economy. However, among independents that is 28 percent.
But when it comes to the confidence Americans have in their lawmakers, they still support Democrats, according to an ABC News/ Washington Post poll from last week.
Some 43 percent of respondents have confidence in Democratic members of Congress, but just 29 percent of voters felt the same way about Republicans.