The 6-foot-1 Chambers, a skillful boxer who rarely weighs more than 210 pounds when he enters the ring, has beaten contenders Dominick Guinn, Calvin Brock and Alexander Dimitrenko as well as former beltholder Samuel Peter — all of whom were taller and heavier.
Chambers won five consecutive fights after he was outpointed by the much-taller Povetkin in 2008 to earn a shot at Klitschko, who dominated and then stopped the Philadelphian with five seconds left in the 12th and final round in March of last year.
Chambers was at a five-inch height disadvantage and out-weighed 244-to-209 by the 6-6 Klitschko, whose trainer, Emanuel Steward, has since maintained communication as an adviser and strategy consultant to Chambers.
"Coming up with a strategy against Eddie was one of the most-difficult things to develop, because as small as Eddie is, he can walk you down and be a little bully and destroy you with short punches," Steward said of Chambers.
"Eddie still is one of the most-feared fighters in the division, so I just really don't think nor do I see his lack of size as being a factor."
The 29-year-old Chambers (36-2, 18 knockouts) will be at a major size disadvantage again when he meets 6-5 Tony Thompson (36-2, 24 KOs) in an IBF heavyweight title eliminator in October that could yield a rematch with Klitschko.
In addition to being a southpaw, the 39-year-old Thompson weighed nearly 256 pounds for his last fight in May, when he stopped Maurice Harris in the third round – his fifth consecutive KO.
"I'm always going for the knockout, but Eddie will present some different problems for me as a smaller fighter," said Thompson, who turns 40 on Oct. 18 and last lost when Klitschko stopped him in 11 rounds in 2008.
"I'm going to have to be patient and stay in position to counter his speed. So I think that it will be his speed against my power, and I think that it will be a knockout."
But that won't be an easy task against Chambers, whose skills were once a challenge during sparring sessions with Klitschko before the Ukrainian’s victory over Calvin Brock in 2008.
"Prepping for Eddie is a lot of work because he can just do so many things," said Steward. "Eddie can move around and change up and move to the side, punch and get in and out."
Chambers was out-weighed 237-to-208 during his most-recent appearance in the ring, a 12-round decision over Derric Rossy in February. Chambers also beat Rossy in 2007, stopping him in the seven round.
"I've proven myself time and time again, and when you're a tough fighter to face like I am, it makes it difficult to match you because guys don't want to fight you — especially in our heavyweight division," said Chambers, who rebounded from the loss to Klitschko against Rossy.
"I think that it would be a lot better if you had to fight the next guy in front of you, but people are in the business of keeping their rankings. I feel there are other options out there, but, you know, not everyone is lining up to fight me."
It is for that reason that Chambers has mulled a drop into the cruiser weight division, whose titeholders are Steve Cunningham (IBF), Marco Huck (WBO), Krzysztof Wlodarczyk (WBC) and Guillermo Jones (WBA).
Former light heavyweight beltholder Antonio Tarver's recent knockout of Roy Jones-conqueror Danny Green also has injected life into the 200-pound division.
"Maybe one of these days, in the future, the cruiser weight division could be a hot commodity,” said Chambers. “So there are all kinds of opportunities out here, and that's another one of them — fighting Antonio Tarver or one of the other guys in that division as well.
"There's some guys who may take a look at that — myself included — although this is all talk and speculation that there may be a possibility that I would do that."
Despite weighing 223 pounds — his career high is 224 — Chambers came up with a majority decision over the 265-pound Peter in March of 2009.
Chambers was in excellent condition against the 6-7, 254-pound Dimitrenko, weighing in at 208 for a majority decision victory in July 2009 that set him up as the mandatory challenger to Klitschko.
Chambers twice floored his rival — with a body shot and a left hook – on the way to handing Dimitrenko his first loss in 30 bouts before a crowd partisan to Dimitrenko in Hamburg, Germany.
"Eddie has extremely good coordination. He's one of the few guys who can block a punch and then hit you with the same right hand that he blocked the punch with. Plus he has great upper body movement," said Steward.
Klitschko (56-3, 49 KOs) has a 14 fight winning streak that includes 10 knockouts as holder of the IBF, WBA, WBO and IBO belts. His older brother, Vitali Klitschko, has won 10 straight with eight stoppages as owner of the WBC strap.
Chambers, nevertheless, still believes that he can dethrone either of them.
"I believe that no matter what, I'm the best in this division besides the Klitschko brothers," said Chambers. "And I still believe that I can beat them as well."
Lem Satterfield can be reached at email@example.com