This game marks the first time both Chris Redfield and Leon S. Kennedy share starring roles.  In fact, they meet and work together.

This game contains many references or homages the older games. These are Leon and Sherry getting separated by an exploding truck (in RE 2 Leon and Claire get separated by an exploding truck), Ada saves a Leon by giving him a key to a vehicle (in RE 4 Ada gives Leon a key to a jet ski), Chris battles a giant snake (he fought a giant snake in the first game), In certain areas the camera will changed to a fixed camera angle (the originals had a fixed camera angle gameplay ), and many others.

This is the first Resident Evil game to be rated M for Mature partially for nudity.

This is in fact the second Resident Evil game where you can walk and shoot. You can walk and shoot in Resident Evil Outbreak 2, which came out 8 years before this.

In November of 2015 a rumor spread that Resident Evil 6 was receiving an Xbox One and PlayStation 4 remaster. Then on February 25th, 2016 Capcom officially announced that Resident Evil 6, 5, and 4 were all being remastered for the PlayStation 4 and Xbox One. On March 29th, 2016 the Resident Evil 6 remaster was digitally released for $20. This remaster turned out to basically just be a port of the PC version on its highest settings though, seeing as it's virtually identical to that version. The only note worthy improvements over the original Xbox 360 and PlayStation 3 versions are: a bump to 1080p resolution, a jump to a 60 frames per second refresh rate, and the inclusion of all the previously released DLC.

Each mutation done by the Enhanced C-Virus reflects the infectee.

Simmons a canine monster, dinosaur and fly in each successive fight. The canine reflected his lust for Ada, the dinosaur reflecting blind rage and the fly representing his stubborn refusal to stay down.

Carla turns into slime that spawns copies of Ada. Reflecting how she was broken down and turned into a clone, resulting in her losing any semblance of sanity.

Piers always saw himself as an expendable tool. Which is why his arm turned into a monstrous weapon that drained his life energy.

The reason Carla wears blue may be a safety measure as she knows the real Ada wears red clothes. She likely told her J'avo troopers to shoot the Ada in red, since it would make it easier.

The "Staying Alive" trophy is a shout out to a disco song of the same name, famously sung by the Bee Gees on the Saturday Night Fever soundtrack.

The "Big Trouble in China" trophy is a shout out to Big Trouble in Little China, a cult classic movie starring Kurt Russell.

The "Kung Fu Fighting" trophy is a shout out to a famous one-hit wonder of the same name, sung by Carl Douglas in 1974.

One of the Leon lines "Welcome back, stranger", is reference to an iconic merchant line from Resident Evil 4.

The Elephant Killer Magnum is refence name from one of merchant's line from Resident Evil 4 when leon buying handcannon, wondered if it would be used for hunting elephant. The line is like this : "Stranger? (Laugh) What do you need that for? Goin' huntin' an elephant?"

Mistakes

In Chris's campaign, all items collected from Chapter 2 (which is flashbacks from Edonia) appear in Chapter 3. Also in Chapter 2, some certain characters can be killed despite being alive in the next 6 months.

Both Ada Wong and Leon/Helena watched the 'Happy Birthday Ada Wong' tape, yet neither one of them rewound it, and all of them watched it from the beginning.

The grenade launcher fires projectiles that have a flat trajectory. Grenade launchers fire projectiles in a curved trajectory.

Leon breaks into a military Humvee to get medical supplies. He does this by breaking a window. Military Humvees invariably have bulletproof windows.

The chainsaw monster disappears from one area and reappears in the next when Leon and Helena are on the raft.

The amount of C4 explosive that Chris puts on a gate to blow it up is far more than enough to blow the gate off its hinges; it could also blow him and Piers up as well as blow a hole in the side of the building they are in.

The Player is somehow able to use rifle ammunition in his pistol. Rifle ammunition imparts too much recoil to be used in a pistol.

Neither Jake nor Sherry show any signs of growing hair despite being held captivated for 6 months.

Jake and Sherry easily retrieve their firearms from a normal-looking locker, including all of their supplies from the past six months. This is highly unusual considering that they are held captive in a place guarded with a high security system (which also has electronic locks) and armed J'avos.

A valve on the submarine rotates to the left to shut off water. Valves need to be rotated to the right to be shut off.

In the underground laboratory, Leon inexplicably empties a sink by turning on the faucet.

The searchlights on the carrier do not track the Harrier at any time.

The first aircraft carrier has a pit of molten metal aboard. There is no reason for an aircraft carrier to have this.

Finn blows an entire rail car which must weigh many tons completely off the ground. It would take more explosives than a man could carry to do this.

Enemies at the beginning of chapters that have weapons do not drop weapons or ammunition when dispatched.

When the Player opens a bulkhead door with a wheel, the locking mechanism doesn't move.

The aero planes that drop paratroopers on the bridge are too low to safely drop paratroopers, not to mention being too slow to fly.

If a player character fires his weapon in the cutscenes, the ammunition stays the same.

Controls can activate before the player character touches them.

The movable bins of scrap metal sometimes do not have their forklift pockets aligned outward, meaning that a forklift or other such vehicle would not have been able to put them up there.

Despite sinking rear-end-first, the submarine still has stairs oriented perpendicular to the rear end.

When shooting at a monster in a cutscene during Jake's campaign, Jake can be heard firing a round, but he cannot be seen shooting at the monster.

In the banquet hall there are candles burning even though no one could possibly have lit them yet.

Leon kills a zombie with a knife and then leaves the knife within the zombie's head. Although Leon has another knife, it does not make any tactical sense to not keep both knives.

In pursuing Ada Wong, neither Chris nor Piers seem to be aware that she wears totally different clothing from Carla.

Leon is told that there is an elevator leading to a parking garage. Despite this, he later asks how to leave the building and is told this again.

In spite of being a mercenary, Jake is only armed with a pistol and no extra ammunition for it at the start of his campaign.

Chris tells Piers to take out 'those' missiles even though there is only one.