The 70th annual edition of the tournament began on March 18, 2008, and concluded with the championship game on April 7, at the Alamodome in San Antonio, Texas.

Kansas, however, spoiled their national championship hopes by handing the Tigers their second loss of the season, winning the game in overtime, 75–68.

Memphis's entire season was later vacated by the NCAA due to eligibility concerns surrounding freshman guard Derrick Rose.

American University (Patriot), UMBC (America East), Texas–Arlington (Southland), and Portland State (Big Sky) all entered the tournament for the first time in their school's history.

The sub-regional pod played at the St. Pete Times Forum in Tampa, Florida, featured four games where a double digit seed won.

The other was #10 seed Davidson, who rode the hot shooting of Stephen Curry to defeat Gonzaga, Georgetown, and Wisconsin before nearly upsetting Kansas in the regional final.

USC vacated all 21 of its wins and its appearance in the 2008 NCAA tournament due to sanctions from the University of Southern California athletics scandal.

Bracket Source Memphis' entire 2007–08 schedule results were vacated due to NCAA sanctions involving the eligibility of Derrick Rose.

Their high scoring tied the mark for second most in North Carolina tournament history, aided by Tyler Hansbrough and Ty Lawson's 21 points each.

[17] In the same pod, fourth seeded Washington State defeated 13th-seed Winthrop 71–40, holding them to 11 points in the second half and leaving them far behind after a 25–1 run.

American's star player, Garrison Carr, led his team with 26 points, tying the game at 40 with 11 minutes to go before Tennessee went on a 10–0 run to score the win.

Instead, Notre Dame shot 24% from the field, their worst offensive effort since 1983 and the fifth-worst in the history of the NCAA tournament's opening rounds.

In reality, while Beasley and Mayo did well, it was the other K-State players who made the difference, applying a strong defense to the Men of Troy's attack and coming up with the school's first tournament win since 1988.

[32] Earlier that day in Omaha, ninth seed Kent State tied an NCAA Tournament record for scoring lows with their 10 points in one half against UNLV.

[38] The following afternoon, the 12th-seeded Villanova Wildcats defeated the 13th-seeded Siena Saints in a 12-seed versus 13-seed Cinderella match-up by a score of 84–72 to reach their third Sweet 16 in four years.

[39] Tenth-seeded Davidson became the second double-digit seed to advance to the Sweet Sixteen hours after Villanova's victory, ousting second-seeded Georgetown 74–70, to play Wisconsin in the other regional semifinal.

The Wisconsin defense, best in the nation at points allowed with 53.9, remained close until early in the second half, when some key steals and Davidson threes pulled the Wildcats far ahead.

Kentucky got to within two points with 22 seconds remaining, but two Marquette free throws and a late steal handed the Wildcats an early tournament loss.

[48] They met third seed Stanford in the next round, who handily defeated 14th-seeded Cornell 77–53, never trailing the entire game, and never allowing the Big Red to get closer than 18 points in the second half.

[51] Third-seeded Stanford saw Brook Lopez make the difference in overtime with a basket with 1.3 seconds left to beat Marquette 82–81 and advance to Houston, Texas.

The game was extremely physical and hard-fought, with the Panther coming back from 10 down to take the lead in the middle of the second half, only to see it vanish in the final minutes with help from eight straight points from the Spartan's Drew Neitzel.

Stanford made things close at about the 13 minute mark of the second half, bringing it to within one at 52–51, but Texas went on a 16–2 run and turned the game into a rout.

[61] The top seeded UCLA Bruins set several records in their win against 16th-seeded Mississippi Valley State at Anaheim, California, holding them to 29 points in a 70–29 victory.

[72] The ensuing dunk by UCLA's Russell Westbrook was later waved off by officials as occurring after time had expired, making the final score 51–49.

Raymond scored all eight of his points in the bonus round after being held scoreless in regulation, and poor free-throw shooting by the Mountaineers, missing four out of six free throws, sealed the victory.

[76] UCLA was the first team to advance to the Final Four in San Antonio, Texas, the third straight year and the 18th time in school history they have done it, with a 76–57 victory over Xavier.

The complete list of announcing teams follows: Greg Gumbel once again served as the studio host, joined by analysts Clark Kellogg and Seth Davis.

For the first time since the rights were acquired, the host team spent the entire tournament at the CBS Broadcast Center in New York City and did not travel to the Final Four site.

This allowed access to all tournament games in the first three rounds of the main draw not shown on the local CBS station in the viewer's area.

The ads were not the same as those shown on television, and there was a separate halftime show hosted by Jason Horowitz joined by analysts including St. John's head basketball coach Norm Roberts.