A close friend of Brian Cowen's, the former Enterprise Minister's star ascended in line with the Tullamore Taoiseach's.
From Cullen, Co Cork, Mr O'Keeffe graduated from UCC and worked as a lecturer at Cork IT before entering politics.
He was a Cork county councillor from 1985 and also chaired the Southern Health Board for a time. First elected to the Dail in 1987, he lost his seat two years later to a young party upstart called Micheal Martin, though he was appointed to the Seanad.
He didn't let that happen twice. From 1992, Mr O'Keeffe was re-elected every time.
Over the years, he was a member of Oireachtas committees but generally a backbencher, though he was a junior minister under Bertie Ahern in 2004. When Cowen became Taoiseach in 2008, he made Mr O'Keeffe Minister for Education.
The current era of austerity meant O'Keeffe had to make cuts, increasing class sizes and reducing minority faith school funds. In March 2010, he was promoted to the Enterprise Minister post. In the face of mounting unemployment and business closures, his enthusiasm and engagement were undeniable.
But in January last year, Mr O'Keeffe announced he wouldn't run in the March election, resigning his ministership and retiring from politics. At 66, local sources say he is "not the retiring kind" but is "in retirement mode" -- for now.
Married to Mary Murphy, they have four grown-up children.
Sunday Indo Business