In Arizona, veteran quarterback Carson Palmer is hoping to lead the Cardinals into the National Conference championship game after battling back from what many feared would be a career-ending second knee injury in 2014.
Meanwhile at Foxborough on Saturday, Kansas City Chiefs safety Eric Berry will aim to upset Tom Brady and the New England Patriots just over a year after being diagnosed with cancer.
Palmer's re-emergence as one of the best quarterbacks in the NFL at the age of 36 has been a story of redemption more than a decade in the making.
The number one pick in the 2003 draft, Palmer spent a frustrating first decade in the NFL, his early promise with the Cincinnati Bengals derailed by a serious knee injury in a 2006 playoff defeat to the Pittsburgh Steelers.
The injury left Palmer with torn anterior cruciate and medial collateral ligaments as well as damage to cartilage and the kneecap.
"On a scale of one to three, this is a four," declared the surgeon who operated on the injury. After a complete knee reconstruction, Palmer made a successful return the following season and earned selection to the Pro Bowl.
- Second knee injury -
But several more seasons of frustration followed before he reportedly retired in 2011. Out of favor with the Bengals, he was eventually traded that year to the Oakland Raiders where he played two seasons before landing at the Cardinals.
Palmer threw for a then career-best 4,274 yards in his debut season in Arizona in 2013 but suffered another agonizing knee injury in 2014 that left him facing a bleak future.
After yet more surgery and intense rehabilitation, Palmer returned this year to deliver the best numbers of his career.
He finished the regular season with a career high 35 touchdown passes and 4,671 yards as the Cardinals went 13-3 to earn the NFC second seeding.
"It's the most exciting time of my career," Palmer told Sports Illustrated.
"It's the most fun I've had playing the game. It's the most free I've felt," added Palmer ahead of the Cardinals meeting with the Green Bay Packers in Phoenix on Saturday.
Eric Berry's journey to this weekend's meeting with the Patriots, meanwhile, has been borderline miraculous.
Diagnosed with Hodgkin's lymphoma in late 2014, Berry battled through a grueling regime of chemotherapy last year to be declared cancer-free, allowing him to return to the Chiefs for pre-season training.
- Agonizing recovery -
His inspirational performance in the Kansas City defense has earned him selection to the Pro Bowl, and he was instrumental in kickstarting last weekend's rout of the Houston Texans with an early interception.
Berry revealed he had inched his way back to fitness in an agonizing recovery.
"One of my goals used to be to do five push-ups," Berry said last month.
"So to go from doing five push-ups to being out on the field with my teammates is a long way. There would be times where I would work out and just be crying after the workout just because I couldn't believe I made it through and it was that hard," he told SportingNews.com.
"I couldn't push myself like I wanted to. I had to understand that everything wasn't going to come back every night ... Going through chemo is a monster. You literally feel like you're dying every day.
"When you look at it, you're not battling the chemo, you're battling yourself the whole time. It was me versus me," he said.
"There were many times where I didn't know if I would wake up tomorrow. I would just be up, scared to go to sleep."
Chiefs coach Andy Reid said team officials had remained confident Berry would make a recovery, citing the player's determined personality.
"He was so driven that way that you kind of had the feeling he was going to get there, as crazy as it sounds.
"But when you look back on it now that it's real, what a great story. True toughness and grit to be able to do that." AFP