More than any player of the past decade, Peyton Manning's strengths and weaknesses have been heavily documented. Though his struggles with the 3-4 defense early in his career have been well documented, Manning mastered the 4-3 defense very early in his career.
This Sunday, Manning well get to square off against the New Orleans Saints and their 4-3 defense. The 4-3 is build around a blitzing front line and a strong secondary that induces turnovers. Part of the reason Manning has been so successful against the 4-3 in the past five seasons is because Manning responds well to the blitz, and doesn't really cause too many turnovers.
In the past five seasons (since 2005), the Colts have only lost to a 4-3 defense only 6 times when playing all of their starters. Of those six losses only one was too a non-divisional opponent, the 2008 Chicago Bears on opening day. If you recall, the Colts started 2008 very slow because Peyton Manning missed all out training camp with a knee infection that he was still recovering from early in 2009.
Much of Manning's success against the 4-3 stems from the fact that the Colts have run the 4-3 for Manning's entire career, so he has seen it every day. Since 2005, the Colts have run one of the most effective 4-3's in the NFL. Even when the Colts defense was bad, Manning still had Tony Dungy as his head coach, one of the revolutionaries of the 4-3 Cover 2 defense. To put it plainly, Manning understands the 4-3 defense better than any quarterback in the NFL. Then again, Manning probably understands every defensive formation and scheme better than every other quarterback in the NFL.
So when the Colts line up on offense tomorrow, look for Manning to feel the Saints out early, before going ballistic on their 4-3 scheme tomorrow. The only difference between this Saints team and the other 4-3's that Manning has played in the past is the fact that the Saints offense is extremely potent. Much like when Manning faces the Houston Texans, he won't have much time to adjust to the Saints defense before he'll find himself in an early hole.