The departure of Alan Milburn from the government is a big political surprise.
Milburn is seen as a leading Blairite
The former health secretary was seen as a leading Blairite and tipped by some as a future Labour leader.
One of the prime minister's most energetic ministers, he was regarded in Westminster he was regarded as highly ambitious.
There had been speculation that he wanted to leave the health department and move to a new role within the cabinet.
But he has quit the government saying he was finding it difficult to balance his political work with raising a young family - he has two sons - in the north east.
The MP said he had discussed the situation with his partner Ruth over the last 12 months.
Mr Milburn was born on 27 January 1958 and educated at John Marlay School, Newcastle, and Stokesley comprehensive in Cleveland, before going to read history at Lancaster University.
Born 1958 in Birmingham
Educated at John Morley School, Newcastle and Stokesley Comprehensive
Graduated in history from Lancaster university
Co-ordinator at Trade Union Studies Information Centre
Business development officer, North Tyneside Council 1990-92
MP for Darlington 1992
Opposition treasury spokesman
Chief Secretary to the Treasury 1998
Secretary of State for Health 1999
Raised by a single mother, he cut his political teeth by fighting for shipbuilding and steel jobs on Tyneside and a raft of other campaigns.
He worked in a Marxist bookshop called Days of Hope for £20 a week and was a CND activist.
He ran the campaign to save Sunderland's shipyards and is a past president of
the Union for Manufacturing, Science and Finance in the North East.
Mr Milburn decided to join the Labour Party in 1983, becoming MP for Darlington in 1992 after a career in trade unionism and local government.
He rose swiftly once Labour came to power in 1997, first as a health minister, and was one of Tony Blair's most highly trusted ministers, having been promoted to become health secretary following Frank Dobson's resignation in 1999.
Mr Milburn in his days as a young radical
He had moved into that position after working alongside Gordon Brown as chief secretary to the Treasury.
And he had a bruising battle with Mr Brown over the controversial foundation hospitals plan.
The chancellor opposed the moves and Tony Blair had to intervene in the clash between him and Mr Milburn.
And the health secretary took a lot of flak over the proposals, acting as a barrier between Mr Blair and the criticism.
'Passion and humour'
There is concern in the Labour rank and file that the foundation hospital proposals will create a two-tier health service.
But his "true passion" for the NHS and his "special blend of vision, passion and humour" was hailed on Thursday by Gill Morgan, chief executive of the NHS Confederation, which represents health service managers.
"The NHS will miss his powerful support and advocacy," she said.
She said he had helped the health service move forward with a "powerful vision about a more devolved health service and a real
understanding of the issues facing those at the NHS frontline".