This weekend, however, the American will walk through the gates of Roland Garros for the first time since 2004 carrying the hopes of American women's tennis on her shoulders after a remarkable surge from the tennis wilderness.
When the 25-year-old Serena ended last year ranked 95th in the world it seemed the weapons of destruction that had made her the most feared player in women's tennis had been decommissioned for good.
Knee injury after knee injury, problems with her weight and a growing sense that her life's focus was on acting rather than the narrow confines of tennis had many predicting the more fiery of the Williams dynasty would fade away into the shadows.
With her older sister Venus also struggling down at 48 in the rankings and old sparring partner Lindsay Davenport off starting a family, American women's tennis appeared to be coming to the end of a glorious era in which the trio bagged 15 grand slam titles and dominated the world number one spot.
The Australian Open changed all that.
She came from way off the radar to become the third lowest ranked player since the inception of rankings to win a major, demolishing Russia's Maria Sharapova in a one-sided Melbourne final.
Serena repeated her thrashing of Sharapova in Miami on her way to winning the Sony Ericsson title. In the final she lost the first set to world number one Justine Henin 6-0 before storming back to stun the Belgian.
'REALLY CONFIDENT' Despite a quarter-final loss at the Italian Open last week she is back inside the world's top 10 and represents surely the best chance of American success in Paris where she won in 2002 en route to the ''Serena Slam''.
''I feel like I'm really going to enjoy myself there,'' Serena said after her Rome defeat. ''I'm really confident. I feel that I'm getting there fitness-wise and that I can hit a lot of balls.
''I always say that when I'm playing well, no one can beat me. I'm not just saying that to sound full of myself or anything, but it's true.'' Venus has only been beyond the quarter-finals once at the French Open, in 2002 when she was beaten by her sister, and her patchy form this year hardly makes her a leading contender.
Then again, as she proved by winning Wimbledon in 2005 as the 14th seed, nothing can be taken for granted when the Williams sisters are in town.
On the American men's side, Andy Roddick could only be notionally labelled a challenger based on his world number three ranking. He has won just four matches on the Parisian claycourts in six visits and would happily fast forward a few weeks, such is his torment on the slippery red stuff.
American number two James Blake's claycourt credentials are only marginally more impressive and he did reach the semi-finals on the slow surface in Houston last month.
Both will be targeting Wimbledon and the U.S Open later this year for a serious crack at ending the American men's four-year wait for a grand slam title.
Reuters AKD VV0957