A battle of two NFC playoff teams from a season ago, this weekend's SNF matchup promises to come down to the wire at Candlestick Park, where the Niners went 7-1 during the 2011 regular season.
The Lions were 5-3 on the road last year and are capable of springing an upset on the home team.
Here we get you set for everything you need to know to catch the hard-hitting action on the gridiron Sunday night on NBC.
When: Sunday, September 16
Where: Candlestick Park, San Francisco, CA
Start Time: 8:20 p.m. ET
The Post-Game Handshake
Everyone remembers the awkward postgame tough-guy impressions from Jim Harbaugh and Jim Schwartz the last time the Lions and Niners met up in 2011.
Here it is in case you missed it (at the 0:30 mark).
The two teams have not played since that uncomfortable exchange in Week 6 last October.
Regardless of which side wins on Sunday night, I'll be most intrigued by the postgame reunion of the two Jims.
Will the Niners Slow the Lions?
The Detroit Lions boast the NFL's No. 1-ranked passing attack after one week this season. Lions quarterback Matthew Stafford threw for 355 yards and a touchdown in Week 1 against the Rams, but also showed some vulnerability in throwing three picks.
He'll face a much tougher defense in the 49ers this Sunday night on the road, however.
That bodes well for their chances this weekend.
Whichever side wins this key matchup in Sunday night's showdown will be headed to a 2-0 start on the season. It will be up to the San Francisco defense, however, to slow the Detroit aerial assault in Week 2.
If it doesn't, the Niners will be in a world of trouble if they wind up in a shootout with the Lions.
Follow Bleacher Report Featured Columnist Patrick Clarke on Twitter for more NFL take, reaction and analysis.