The Baltimore Ravens will try to put the furore over the Ray Rice scandal behind them with victory over the Pittsburgh Steelers.
Star running-back Rice was released by the Ravens and suspended indefinitely by the NFL after a new video emerged on Monday of him striking his then fiancee and now wife Janay in an elevator at a casino in Atlantic City in February.
Rice had been banned for the opening two games of the new season after being charged with aggravated assault, but that punishment was criticised as overly light, with the public outcry sparked by the release of the new footage leaving the Ravens and the NFL with little choice but to impose the severest of sanctions.
John Harbaugh's men are to remain in the spotlight as they bid to bounce back from a season-opening 23-16 defeat to the Cincinnati Bengals with a nationally televised Thursday night game with another AFC North rival in the Steelers.
Harbaugh's brother Jim will be able to coach under more serene circumstances on Sunday as his San Francisco 49ers take on the Chicago Bears in the first regular season game at their new Levi's Stadium home following a fine 28-17 victory over the Dallas Cowboys.
San Francisco's NFC West counterparts the Seattle Seahawks continue their quest to retain the Super Bowl title with a visit to the San Diego Chargers. The Denver Broncos, last season's runners-up, take on the Kansas City Chiefs.
Away from the Rice saga it is injuries that have dominated the headlines, with a number of teams heading into week two without key players.
The Houston Texans will be minus the services of defensive end and first overall draft pick Jadeveon Clowney for their clash with the Oakland Raiders due to a knee injury, while running-backs Doug Martin of the Tampa Bay Buccaneers and Ben Tate of the Cleveland Browns could both miss out with similar problems for their respective games with the St Louis Rams and the New Orleans Saints.
The Saints, who lost an overtime thriller to the Atlanta Falcons 37-34, are one of a number of assumed Super Bowl contenders that will be seeking to atone for a week one loss.
Tom Brady and the New England Patriots visit the Minnesota Vikings on the back of a 33-20 loss to the Miami Dolphins, the Indianapolis Colts host the Philadelphia Eagles on the back of a 31-24 reverse at Denver and the news that linebacker Robert Mathis - serving a four-game ban for violating the league's performance-enhancing drugs policy - is out for the season with a torn Achilles tendon.
The Green Bay Packers battle the New York Jets at Lambeau Field following a 36-16 hammering by the Seahawks, while quarterback Cam Newton will start for the Carolina Panthers against the Detroit Lions after missing the 20-14 success at the Buccaneers with a rib injury.
Elsewhere, the Falcons and Bengals face off in Cincinnati, the Tennessee Titans meet the Cowboys, the New York Giants take on the Arizona Cardinals, the Buffalo Bills host the Dolphins and the Jacksonville Jaguars travel to Washington to clash with the Redskins.