On one side for St. Louis will be a former All-Star and Cy Young Award runner-up still looking to find his form following surgery that cost him all of the 2011 season.
For Colorado, it turns to its Opening Day starter who is now trying to fight his way back into the rotation.
That is the pitching matchup on tap tonight when the Cardinals and Rockies continue their four-game series.
Getting the call for the Cards is Adam Wainwright, who is 6-8 with a 4.75 earned run average in 16 starts this year after missing all of last season because of Tommy John surgery.
A 20-game winner in 2010, the right-handed Wainwright is coming off a loss to the Pirates on Sunday, when he allowed a season-high 11 hits and matched a season worst with seven runs while giving up a pair of homers over five innings. It did, however, mark just the second time in nine starts that Wainwright allowed more than three runs.
"I was able to keep cool between innings and I felt like I was refreshed when I went back out there each time," Wainwright said about dealing with the heat in the home start. "Tonight was just one of those horrible nights when I didn't make pitches when I needed to."
The 30-year-old does have good career numbers versus the Rockies, going 3-1 with a 1.44 ERA in eight meetings (4 starts).
The Rockies will give Jeremy Guthrie another shot in the rotation as he gets his first start since June 17 at Detroit, where he allowed four runs -- three earned -- on eight hits and two walks over just three innings. That was a far cry from his Opening Day victory over the Astros on April 6 and the righty has won just twice since.
He threw 12 1/3 innings over four appearances out of the bullpen, going 0-1 and picking up a blown save on Monday against San Diego.
The humble 33-year-old is just grateful for another chance to start.
"It's another opportunity, and I know in baseball nothing is guaranteed, no matter how much experience you have, what you may or may not have accomplished," Guthrie said on Colorado's website. "I've taken every outing, whether they've been good outings or bad outings, and been grateful for them. I continue to feel the same way. I have a chance to start again, and hopefully that will lead to many, many, many more starts."
Guthrie is 3-7 with a 6.56 ERA in 15 games this season, including 11 starts, and will face the Cardinals for the first time in his career.
The Rockies drew even in this series with Tuesday's 3-2 victory. All of the runs came on two swings of the bat as St. Louis' Matt Holliday hit a two-run homer in the first before Colorado received a three-run homer by Tyler Colvin in the third to snap a three-game slide despite registering just five hits as a team.
"I just threw it bad," said Cardinals starter Joe Kelly of his 0-2 pitch to Colvin. "It's something you gotta either bounce in the dirt or get it more off and I didn't do both of those and it ended up as a three-run homer."
Kelly threw six innings to absorb the loss, while Jeff Francis got the win for the Rockies with his five-inning start.
"I made a pitch to Matt that he hit over the fence," admitted Francis, who was teammates with Holliday from 2004-08 in Colorado. "I was running out of pitches to throw him by the end of the game."
St. Louis lost for the fourth time in six games and is 2 1/2 games out of first place in the National League Central.
The Rockies improved to 3-9 in their past 12 versus the Cardinals and won for only the second time in their last nine at St. Louis over that span.