The action begins in the early hours of Friday with Sky Sports coverage of the Buffalo Bills and Miami Dolphins. It ends in the early hours of Tuesday, with the BBC's coverage of the Chicago Bears and San Francisco 49ers.
Here are the best individual matchups from Week 11's televised games.
Miami Dolphins at Buffalo Bills, Sky Sports 2, Friday, 1.00am
Karlos Dansby vs. C.J. Spiller
The Bills need a big game from running back C.J. Spiller, to get the better of old foe the Dolphins.
Buffalo will be without the injured Fred Jackson, so Spiller gets his chance to carry the full load. The 2010 first round pick is more dynamic than Jackson.
He offers legitimate game-breaking speed, evidenced by his eye-popping 7.3 yards per carry average. If he is going to showcase his big play skills, Spiller will need to avoid Miami linebacker Karlos Dansby.
The veteran is the leading tackler for the fifth-best run defense in the NFL. Dansby is an instinctive linebacker who quickly diagnoses plays and fills gaps.
Miami's defensive line must keep Dansby free from blockers, who must corral Spiller before he reaches top speed.
Green Bay Packers at Detroit Lions, Sky Sports 2, Sunday, 5.30pm
Jordy Nelson vs. Chris Houston
If the Detroit Lions hope to save their season against the Green Bay Packers, they must stop receiver Jordy Nelson. That task will fall to cornerback Chris Houston.
Nelson has emerged as the favourite target for quarterback Aaron Rodgers. He is a wide receiver who uses his 6'3" 217-pound frame to separate from coverage.
He runs intelligent and precise routes and always seems to hang onto the ball.
Houston is a gritty veteran who is probably the best cover man for the Lions' ninth-ranked pass defense. The 28-year-old won't be able to outmuscle Nelson, but he must shadow him in the deep zones.
Indianapolis Colts at New England Patriots, Sky Sports 2, Sunday, 9.25pm
Reggie Wayne vs. Kyle Arrington
The Patriots must take away Colts' rookie passer Andrew Luck's best weapon, wide receiver Reggie Wayne. That will require a big game from opportunistic cornerback Kyle Arrington.
Wayne has been the favourite target for Luck. His prolific connection with the first overall draft pick has produced a 6-3 record. Wayne currently leads the league with 69 receptions for 931 yards.
It will be facinating to see what Patriots coach Bill Belichick has in store for a savvy veteran like Wayne. Belichick will need Arrington to deny Wayne a clean release off the line of scrimmage.
Arrington is New England's best cornerback and he must lock Wayne up underneath. If Arrington can win in press coverage, Belichick can help him with a deep safety over the top.
The Patriots must take Luck out of his comfort zone, by forcing him away from Wayne.
Baltimore Ravens at Pittsburgh Steelers, C4, Monday, 1.10am
Ray Rice vs. Lawrence Timmons
With or without Ben Roethlisberger, the latest chapter in the Ravens-Steelers rivalry, is compulsory viewing. This particular round of hostilities could be settled by the matchup between Ray Rice and Lawrence Timmons.
Rice is one of the finest running backs in the league and the real key to Baltimore's offense. His elusive running, clutch receiving and smart pass-blocking skills have frequently frustrated the Steelers.
Ultra-athletic inside linebacker Timmons is Pittsburgh's best answer to Rice. He has the size to stuff the run in the middle and the speed to blitz the edges.
Timmons is also exceptional against the pass. He is the only player the Steelers can trust in man to man coverage against Rice.
Chicago Bears at San Francisco 49ers, BBC iPlayer, Tuesday, 1.30am
Joe Staley vs. Julius Peppers
The Chicago Bears defensive line is one of the toughest in the game and their best lineman is Julius Peppers. Niners' left tackle Joe Staley will be in for a long night, attempting to control the stellar veteran.
It will be the speed of Peppers, versus Staley's bruising strength.
The Bears like to move Peppers across the formation, but he does his best work rushing the edge. Even at 32, he still possesses first step quickness few offensive tackles can handle.
The 11-year pro also has a devilish spin and inside twist moves that could overwhelm Staley. The hulking left tackle struggled against Robert Quinn during last week's 28-28 tie with the St. Louis Rams.
If he can't handle Peppers, then Chicago's rampaging front four could take over this game.
Watch out for these five match ups and how they help decide Week 11's televised games.
image: © Keith Allison