On this occasion the biggest obstacle could prove to be Alberto Contador, the 2007 Tour winner and far and away the most successful of his younger rivals – who just happens to be Armstrong's team-mate.
The latent conflict between the two has been provoked by cycling's central paradox: that it is a team sport which only one person wins. And while it was obvious that Contador would make the Tour his major target of the season, Armstrong, despite the risk of upsetting his team-mate, has consistently refused to rule out doing the same.
Despite how hungry Armstrong was to win before he retired – he would refer to runners-up as "first losers" – the Texan's chances of victory are perhaps less than they were in the past. But they remain considerable. "If Lance is in the condition he says he is, and he's up there after the opening time-trial in Monaco then he can win the Tour," says the 2006 race champion, Oscar Pereiro, of Spain. "And Contador's in the wrong team."
This particular showdown has been a long time coming. Last autumn Contador was halfway towards winning his third major stage race in a row, the Tour of Spain, when he heard it confirmed that Armstrong was making a comeback.
A month later the Texan announced he would be reforging the old alliance between himself and long-standing manager Johan Bruyneel, which meant joining Contador's team, Astana. The Spaniard talked to a couple of rival squads about quitting, but finally remained.
The result is that the Kazakh-financed squad looks ridiculously top heavy, to the point where almost the only question before today's start is not whether an Astana rider can win the Tour, but which one will do so? Apart from Armstrong and Contador, two of the team's other leading lights, Montana-born Levi Leipheimer and German Andreas Klöden, have both taken top three places in the Tour.
That brings Astana's total tally of podium finishes in cycling's Grand Tours – of Italy, France and Spain – to 16. No other team at the Tour start in Monaco has even a third of that total.
However, it is Armstrong and the potential for conflict with a team-mate 11 years his junior that has really gripped cycling fans' attention. Armstrong himself rates Contador as the best stage racer in the world. But that was a title which belonged to the Texan up until his retirement in 2005 and since announcing his comeback Armstrong has slowly but surely moved up the hierarchy of potential Tour winners.
The Texan's main build-up for the summer has been Italy's equivalent race, the Giro. Armstrong finished 12th, which may not sound great, until you remember he had broken his collarbone five weeks before.
What is most intimidating of all for Contador and the rest is Armstrong's Tour record. Twenty four stage wins, 48 days in the yellow jersey and seven outright victories is a total which towers above all others.
All this of course despite a life-threatening brush with cancer which made Armstrong even starting the Tour an achievement. Raising the level of public awareness about the illness, Armstrong says, has been the main reason for his comeback.
However, his crusade has been sadly edged out in the media by the potential for conflict with Contador. Since September, pre-Tour contact between the two has been minimal – squeezed to one day's racing in March and one training camp in November last year.
The official team line, confirmed in yesterday's press conference is that Contador is leader. But it is hard to see that continuing if Armstrong gains time on him in Monaco's opening time-trial, or later.
Simultaneously, the question of who supports which rider amongst the seven other Astana riders has been rife. The American seems certain to count on the support of Leipheimer, a former team-mate back in his US Postal days, while Contador insisted on the presence of one rider known to be loyal to him, Sergio Paulinho.
However, Bruyneel rejected Contador's requests for a second helper, Benjamin Noval, and to maintain the balance of power, kept Armstrong's friend and team-mate Chris Horner out of the Tour team as well.
"Alberto's very hurt about what's happened," Noval told the Spanish press. "Bruyneel told me I wasn't going to race 'for the good of the team'. They don't consider Alberto to be the great rider he is."
The key to it all, though, is perhaps Contador himself. He has largely maintained his silence, but accepts his relationship with Armstrong is "all but non-existent," and that "the race itself will have to decide who is leader, and who works for who."
"I do know it will be more difficult for me to win the Tour than in 2007," he added. Starting this afternoon, Contador is on the point of finding out whether the biggest barrier to a second success is a 37-year-old Texan from his own team.
Tour de force: The men to watch in 2009
Lance Armstrong
Nationality American
Team Astana
Past form Seven Tour wins says it all.
Why he'll win Simple: he's been the most successful Tour de France racer of all time.
Why he won't Too long in the tooth and too long away.
***
Carlos Sastre
Nationality Spanish
Team Cervelo
Past form Won the Tour last year against all expectations.
Why he'll win Everybody will be watching Contador and Armstrong.
Why he won't You can't surprise the opposition twice.
***
Andy Schleck
Nationality Luxembourger
Team Saxo Bank
Past form Best young rider in the Tour last year.
Why he'll win Strong climber. Strong team.
Why he won't Inexperienced and impulsive. Poor time-trialler.
***
Alberto Contador
Nationality Spanish
Team Astana
Past form Won the Tour de France in 2007 and the Tours of Italy and Spain in 2008. Not even Armstrong's done that.
Why he'll win Even Armstrong says Contador's unbeatable on the climbs.
Why he won't Armstrong will out-time-trial him and become the Astana leader.
***
Mark Cavendish
Nationality British
Team Columbia-HTC
Past form The best sprinter of his generation.
Why he'll win Nobody's been able to match him in the final metres for the last 12 months. It's unlikely they'll start now.
Why he won't Bad luck or final kilometre crashes.
***
Denis Menchov
Nationality Russian
Team Rabobank
Past form Has won the Tour of Italy once, the Tour of Spain twice.
Why he'll win Stage-race specialist.
Why he won't Always comes unstuck in the Tour.
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