After he missed last season recovering from neck surgery and was then released by the team he starred with for 13 years, Manning makes his much-anticipated debut with the Denver Broncos against the visiting Steelers on Sunday night in a rematch of last season's playoff thriller.
This will be Manning's first game that counts since Jan. 8, 2011, when Indianapolis lost 17-16 to the New York Jets in an AFC wild-card contest. The future Hall of Famer is trying to downplay his return from multiple neck surgeries while hoping to play well for Denver after the Colts decided to part ways with him.
"I know how hard I've worked to get back to this position and how much time I've put in to rehabbing and how much time I continue to put in," said Manning, a Super Bowl champion and four-time league MVP who started every game for the Colts from 1998-2010.
"I'm going to play as hard as I possibly can, so that's really all I know to do."
Manning and the Broncos will be thrown into the fire against a Pittsburgh team that expects nothing less than the over-the-top hype that's surrounding this contest.
"It was a no-brainer that they were going to put Peyton's first game back on a (Sunday night), and let him play at home," Steelers quarterback Ben Roethlisberger said.
Despite the time off, Pittsburgh also expects Manning to be at his best.
"Guys like him make their reputations in rising up in moments like this," Steelers coach Mike Tomlin said. "He has battled some adversity with injury and being in a new city. We should anticipate his very best. That's what guys like Manning do."
Manning, who is 2-2 - including playoffs - while throwing for 1,079 yards with seven touchdowns and four interceptions against the Steelers, seems excited that his return comes versus a perennial power.
"I've always felt that it's as close to a playoff atmosphere as you can get in the regular season, and playing a tough team like Pittsburgh, playing on prime time, at night, is certainly going to add to the atmosphere," he said.
The Steelers certainly have incentive to play well after losing to the Tim Tebow-led Broncos 29-23 in overtime during last season's wild-card round. Tebow, now making headlines for the Jets, threw an 80-yard touchdown pass to Demaryius Thomas on the first offensive play of overtime to end Pittsburgh's season.
Thomas caught four passes for 204 yards in that contest.
The Steelers were the NFL's stingiest defense, allowing 271.8 yards per game while going 12-4 in 2011. However, linebackers James Harrison (knee) and Jason Worilds (wrist) are banged up, and starting safety Ryan Clark will not play because the sickle cell trait he carries affects him at higher elevations. Harrison is unlikely to play after missing a second straight practice Friday.
One thing Pittsburgh should not expect is for Manning to constantly throw the ball after the Broncos averaged an NFL-best 164.5 rushing yards during their 8-8 season of 2011. Willis McGahee leads the way after running for 1,199 yards last year, while Lance Ball, rookie Ronnie Hillman and former first-round pick Knowshon Moreno also are in the mix.
"Everybody thinks that because Peyton is here we're changing everything," offensive coordinator Mike McCoy said. "But we have a system in place."
While the Broncos feel good about their offense, they will be without their leading tackler in four of the last five seasons as linebacker D.J. Williams serves a six-game drug suspension.
Their first test comes against Pittsburgh, which was third in the AFC last season averaging 389.8 yards but ranked in the bottom half of the NFL with 20.3 points per game.
For the second time in three seasons, Roethlisberger surpassed the 4,000-yard mark (4,077) while throwing 21 touchdowns and 14 interceptions. Roethlisberger, who was 22 of 40 for 289 yards with a TD and an INT at Denver in the playoffs, needs 1,411 yards to surpass Terry Bradshaw as the franchise's all-time leader.
He has the luxury of throwing to Mike Wallace and Antonio Brown, who each recorded more than 1,100 receiving yards in 2011. Wallace, who has caught 132 passes for 2,450 yards and 18 touchdowns over the last two years, will start despite ending his holdout for a new contract last week.
Brown caught six more passes for 284 more yards than Wallace over the final eight games of 2011.
"When given an opportunity, he's done it, and done it in a big way," Tomlin said of Brown, who had five receptions for 70 yards in the playoff loss. "We expect that to continue."
Pittsburgh's backfield situation is less clear-cut.
Though Rashard Mendenhall has made quick progress from a torn ACL suffered in January, the two-time 1,000-yard rusher is doubtful to play. Backup Isaac Redman is nursing a sore hip but expects to play, even indicating Friday he'll split carries with third-year back Jonathan Dwyer.