Amazon Prime's Fallout show is clearly trying to pull in fans of the series, as the recent trailer was full of references to all of the games - even the classics. However, game director Todd Howard says that you won't need to have played the games to get into the show, so it will still work as a jumping-on point if you're completely out of the loop.
This comes from an interview with Den of Geek, in which Howard explains how Bethesda approached the show's creation alongside the future of the game series. He stressed that the show will tell a completely original story from the games, and apparently, not one that you need prior knowledge of the series to enjoy.
"If you’re a fan of the series already, you can jump in and experience the next chapter in Fallout. If you’re not a fan and a bit intimidated by jumping in a game like that, you can experience everything that’s great about this world by clicking your button and enjoying it." - Todd Howard
With that in mind, we shouldn't expect to see many - or possibly any - characters from the games pop up in the show. You might not have to brush up on the lore from the games either, as even with the Brotherhood of Steel looking to play an important role in the story, the show will likely reintroduce them for the benefit of those who haven't played the games before.
Also in the same interview, Howard teased that he had to make changes to the show because it was going to include something planned for Fallout 5. One of the showrunners also commented that they're privy to some information on the next Fallout game, so this proves that Bethesda is at least working on its story right now. Still, we shouldn't expect the game to enter full development until The Elder Scrolls 6 is out of the way, which also won't be for some time now.
In any case, the Fallout show premiers on Amazon Prime on April 11. It's the first Bethesda series to get a big live-action adaptation like this, and it remains to be seen if it resonates with fans in the
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