"I cannot and will not run for the United States Senate in 2010," Biden said in an e-mail to supporters Monday. "I will run for re-election as Attorney General."
Biden's decision ends months of speculation that he would make a bid for the seat held by 36 years by his father and gives Republicans a strong chance to pick up a seat long held by the Democrats. Their likely nominee, Mike Castle, is Delaware's at-large congressman and a former two-term governor of the state.
"The challenges we're facing as a country are extraordinarily difficult," the younger Biden wrote in the e-mail. "The economy. Jobs. Health care. Energy. Education. Climate change. Financial regulation. Foreign policy. These are not only the issues of the moment - they're the issues that will determine our children's future. And as someone who has had the privilege of serving with the bravest men and women on this planet, I care deeply about how we treat our returning veterans and how we resolve our involvement in Iraq and Afghanistan.
"I feel strongly about these issues," he continued. "However, my first responsibilities are here in Delaware. I have a duty to fulfill as Attorney General – and the immediate need to focus on a case of great consequence. And that is what I must do."
Biden's seat is currently held by Ted Kaufman, who was named as an interim replacement for Joe Biden when he stepped down from the Senate after his election in November 2008 as vice president.
National Republicans cheered Monday's news out of Delaware.
"Clearly, Beau Biden's decision not to run for the United States Senate represents a major recruiting setback for national Democrats, who have been counting on his candidacy to keep the Vice President's former seat in Democrat control," said Brian Walsh, spokesman for the National Republican Senatorial Committee. "Regardless of his eventual Democrat opponent, Mike Castle's proven record of independence and bipartisanship puts him in a strong position to win this seat in November."
UPDATE: Kaufman also said Monday he will not run for the seat.
"Serving the people of Delaware in the U.S. Senate is as fulfilling, challenging, and humbling as I imagined when I was appointed," Kaufman said in a statement released by his Senate office. "But as I said at the time, I will not seek election for the balance of the term. I will continue to spend my time as Senator serving the people of Delaware and our nation and not running for office. It is a commitment I made when appointed, and one I will fulfill."
– CNN's Paul Steinhauser and Peter Hamby contributed to this report