The two met in Super Bowl XLIV, with Manning the QB of the Colts.
After a full afternoon of games in Week 8, NFL fans will be treated to an outstanding matchup on Sunday Night Football in Denver featuring two of the game's best quarterbacks in the modern era in Drew Brees and Peyton Manning.
Brees and Manning last squared off in Super Bowl XLIV, when Brees led the Saints to a 31-17 win.
Brees' Saints are coming off a big 35-28 win in Week 7 over the Tampa Bay Buccaneers, as Brees threw for 377 yards and four touchdowns without the services of stud tight end Jimmy Graham.
His team started off the season a dreadful 0-4 without head coach Sean Payton, but they have rebounded for consecutive wins and travel to Denver in a near must-win situation.
Manning's Broncos are fresh off a Week 7 bye following an astounding comeback from a 24-point halftime deficit in San Diego in Week 6.
In that game, Manning shredded the Chargers defense in the second half, going 13-of-14 with three touchdown passes, and the defense forced Phillip Rivers into five second-half turnovers.
Brees is second in the NFL with 18 touchdown passes, while Manning is second in the league with a 105.0 passer rating.
Both have had their obstacles to overcome in 2012. Brees had to adjust to life without Payton calling the plays after he was suspended for all of the 2012 season for his role in Bountygate, and his completion percentage (60.8 percent) has suffered.
Manning, on the other hand, sat out the entire 2011 season because of multiple neck surgeries and some thought he would never take another snap in the NFL.
I believe both players will perform well under the spotlight and put their teams in position to win.
This game, however, may be decided on the defenses and which one makes a play when needed the most.
The New Orleans defense has been dreadful all year, as it is 29th in the NFL in points allowed (30.3) and dead last in the league in yards allowed (465.5).
This game will most likely be a shootout, and the Saints defense may have to stop Manning when he has the ball in his hands and the game on the line.
The Denver defense is middle of the road in points allowed per game (23.0) and 11th in the NFL in yards allowed (330.5). While the stats appear pretty solid, they were exposed by good offenses this year (Texans, Patriots).
The Saints are another team that will expose the Denver defense. However, just like the Saints defense, the Denver defense may need to make only one big play to help secure victory for the home team.
Brees has more weapons and ones he's worked with for longer, while Manning is still seeking to develop better chemistry with his receiving corps. Manning has struggled to find that chemistry at times, but at other times you would think he was throwing to Marvin Harrison and Reggie Wayne.
Who will win this classic duel?
This is a dire situation for the Saints, especially in a loaded NFC. They do not want to fall to 2-5 and further cripple their playoff hopes, as their schedule for the rest of the season does not get much easier.
On the other hand, the Broncos are not in a must-win situation because they are in a weak AFC West that has them in first place at 3-3.
This matchup doesn't have the ring of Brady-Manning, but make no mistake, it will be just as great of a duel between two future Hall of Famers.
Brees Projected Stat Line: 30-of-40, 327 yards, 3 TDs
Manning Projected Stat Line: 27-of-38, 297 yards, 3 TDs, INT
Final Score: Saints 31, Broncos 27