Beau Biden, who followed his father, US vice president Joe Biden, into politics has died of brain cancer less than two years after he was diagnosed.
Beau Biden, who was twice elected attorney general of Delaware, was 46.
He had suffered a series of health problems in recent years, and was admitted to hospital this month at Walter Reed National Military Medical Centre in Washington.
He suffered a mild stroke in 2010 and three years later underwent surgery at a Texas cancer centre to remove what was describe as a small lesion.
He announced last year that he would not seek a third term as attorney general and planned to run for governor in 2016.
"It is with broken hearts that Hallie, Hunter, Ashley, Jill and I announce the passing of our husband, brother and son, Beau, after he battled brain cancer with the same integrity, courage and strength he demonstrated every day of his life," the vice president said, announcing the death of his second child. An infant daughter was killed in a car accident more than four decades ago.
"The entire Biden family is saddened beyond words. We know that Beau's spirit will live on in all of us - especially through his brave wife, Hallie, and two remarkable children," he said.
President Barack Obama said he and his wife, Michelle, were grieving alongside the Biden family.
"Michelle and I humbly pray for the good Lord to watch over Beau Biden, and to protect and comfort his family here on Earth," Mr Obama said.
The vice president said his son had dedicated his life to serving others during stints as a lawyer, a major in the Delaware National Guard and as state attorney general.
Beau Biden served a year-long deployment in Iraq and was awarded a Bronze Star.
He most recently was with the Wilmington, Delaware, law firm Grant & Eisenhofer, where he focused on securities litigation and whistle-blower cases.
"More than his professional accomplishments, Beau measured himself as a husband, father, son and brother," said Joe Biden, who was at his son's side at the time of his death, along with the rest of the Biden family.
"His absolute honour made him a role model for our family. Beau embodied my father's saying that a parent knows success when his child turns out better than he did.
"In the words of the Biden family: Beau Biden was, quite simply, the finest man any of us have ever known."
Beau Biden was first diagnosed with brain cancer in August 2013. He underwent surgery at the University of Texas MD Anderson Cancer Centre in Houston to remove a lesion and was treated with radiation and chemotherapy before doctors gave him a clean bill of health three months later.
He suffered a recurrence of cancer this spring and was admitted to Walter Reed in May, officials said.
Beau Biden gained national prominence after he introduced his father at the Democratic National Convention in Denver on the night in 2008 when Joe Biden accepted the vice presidential nomination. Months later, he returned home from Iraq to see his father sworn into office.
A University of Pennsylvania graduate, Beau Biden earned a law degree from Syracuse University. He was a law clerk for a New Hampshire judge before joining the US justice department from 1995 until 2002, including five years as a federal prosecutor in Philadelphia.
In 2001, he volunteered for an assignment training judges and prosecutors in postwar Kosovo.
With his father, then Delaware's senior US senator, at his side in 2006, Joseph R "Beau" Biden III launched his campaign for attorney general.
He promised to reorganise the state department of justice to better combat identity theft, Internet stalking by paedophiles, street crime and abuse of the elderly.
During the campaign, he sidestepped questions about his ultimate political ambitions.
"Sometimes, it's not good to look too far down the road," said Beau Biden, who was critically injured along with his brother in a 1972 car crash that killed their mother and infant sister. The accident happened just weeks after his father was elected to the US Senate.
Beau Biden remained cautious about discussing his long-range plans after suffering the stroke in 2010.
"Having long-term dreams is a good thing ... but having a plan has never worked for me, because life always intervenes," he said.
Politically astute, photogenic and backed by his father's political machine, he was elected attorney general in 2006 with 52.6% of the vote.
Beau Biden announced in January 2010 that he would not run for the Senate seat his father vacated after being elected vice president in 2008, a decision that stunned political observers and many fellow Democrats.
He is survived by his wife, Hallie, and children Natalie, 11, and Hunter, nine, along with his parents, a brother and sister, a sister-in-law and brother-in-law, and three nieces.
Funeral arrangements were not announced. Beau Biden is entitled to military funeral honours, said Lt Col Len Gratteri, a spokesman for the Delaware National Guard.