The No. 2 seed Kansas Jayhawks (24-9) open their quest for a national championship on Friday afternoon in St. Louis, taking on the dangerous No. 15 seed Eastern Kentucky Colonels (24-9) in South Region action.
These days, it's still somewhat shocking but not unheard of for a No. 15 seed to take on the role of giant-slayer and dash the hopes of one of the big boys. Florida Gulf Coast did it last year, defeating Georgetown and advancing all the way to the Sweet 16.
In 2012, both Duke and Missouri saw their seasons end at the hands of small-conference teams in the second round, losing to Lehigh and Norfolk State, respectively.
So anything can happen, and the Jayhawks can't afford to walk into St. Louis expecting to roll over a spunky, dangerous Colonels team from the Ohio Valley Conference.
Remember, this is March, and anything can happen.
The Jayhawks obviously want to avoid that fate. Even without their big man Joel Embiid, they still have Andrew Wiggins and a ton of offensive talent. But that doesn't mean it'll be easy.
These are the five biggest challenges that Kansas will face against Eastern Kentucky on Friday.