Nelson's votes in the Senate have often placed him at odds with the leadership of his party. A National Journal congressional vote rating from 2006 placed him to the right of five Senate Republicans (Gordon Smith, Olympia Snowe, Arlen Specter, Susan Collins, and Lincoln Chafee). Mary Landrieu was the only other Democrat to place to the right of any Republicans (she placed to the right of Chafee).[50] A similar 2007 National Journal congressional vote rating went even further, placing him to the right of eight Senate Republicans (the above five as well as Richard Lugar, Norm Coleman, and Mike DeWine), with Landrieu once again placing to the right of Chafee and being the only other Democrat to place to the right of any Republicans.[51] Most recently, the American Conservative Union rated his overall performance for 2010 at 48 percent, the highest given to any Democratic senator.[52]
Nelson was one of only two Democratic senators to vote against the Bipartisan Campaign Reform Act of 2002. Nelson is strongly opposed to replacing the income tax with a national sales tax, a position that finds favor with increasingly many conservatives. He has voted with Republicans on matters of bankruptcy reform, environmental protection, lawsuit reform, and trade. In 2004 he was one of only three Democratic senators to vote to invoke cloture on the proposed Federal Marriage Amendment; in 2006 he was one of only two Democratic Senators to vote that way.[53][54] He was the only Democratic senator to vote against a 2006 bill that would have extended federal funding for Stem Cell Research. He has, however, voted consistently against drilling in the Arctic National Wildlife Refuge. He has also opposed President Bush's plan to send an additional 21,500 troops to Iraq.[55] Early in Bush's first term he voted with the majority of his party against scrapping President Bill Clinton's expansive new rules on ergonomics regulation for workers; many of his fellow conservative Democrats like John Breaux, Max Baucus, Blanche Lincoln, and Zell Miller voted with Republicans on the issue. On April 26, 2010, Nelson was one of two Democratic senators in attendance to vote against the motion to move a financial regulations bill forward, siding with Senate Republicans. The other was Harry Reid, who voted against his own proposed bill out of procedure.
On August 5, 2010, Nelson was the only Democrat to vote against Elena Kagan for confirmation to the U.S. Supreme Court.[56]
On December 18, 2010, Nelson voted in favor of the Don't Ask, Don't Tell Repeal Act of 2010.