Webb, who has yet to definitively state whether he is running for re-election, reacted to the ruling with a measured response, saying "I prefer to let this thing play out in the courts."
Meanwhile, the National Republican Senatorial Committee went after Sen. Claire McCaskill (D-Mo.), who is likely to face a very tough re-election campaign in 2012.
"Today's federal court decision serves as yet another reminder that Sen. McCaskill has consistently ignored the views and values of Missouri families, while serving as a loyal rubberstamp for President Obama's out-of-touch agenda," NRSC spokesperson Amber Marchand said in a statement.
Finally, Sen. Orrin Hatch (R-Utah) was also quick to release a statement praising the ruling, and pointing out he was the first senator to argue publicly that the individual mandate is unconstitutional. Vulnerable to a possible challenge from the right, Hatch's response appears to be aimed at shoring up the conservative base.
The Obama administration struck back against the ruling Monday, as a Justice Department spokesperson said the department continued to believe that the law is constitutional.
House Speaker Nancy Pelosi (D-Calif.) echoed that sentiment, saying the ruling "stands in stark contrast to 14 similar challenges to the Affordable Care Act -- in two, federal district judges strongly upheld the law; in the other 12, the challenges have been dismissed."
With a slew of Republicans who ran on a platform of fighting to repeal the health care law set to take office in Congress in less than a month, future debates and developments pertaining to the law likely won't be in short supply as time goes on and the 2012 election grows near.
"There have been and will continue to be a wide range of attempts to weaken this law," said Pelosi. "But as in previous court rulings across the country, I am confident that the Affordable Care Act will ultimately be sustained and will keep benefiting our middle class, our families, and our businesses, indeed every American."
From a political standpoint, the debate will matter most in swing states likely to influence the 2012 presidential election. McCaskill and Webb reside in states that are very important to Obama's re-election prospects, as he won Virginia in 2008 by about 6 percent over Sen. John McCain (R-Ariz.) and narrowly lost Missouri by less than one point. The way the law is viewed in the two states will no doubt, at least in part, shape the way Obama is perceived there.