SPOILER WARNING: Major spoilers from the latest episode of AMC's "Preacher" (and the Vertigo comic series it's adapted from) follow.
In Garth Ennis and Steve Dillon's "Preacher" comics, Jesse Custer is in touch with a spiritual being even before Genesis enters his body. That would be John Wayne, or at least his conscience manifesting itself as John Wayne. Throughout the series, the Duke acts as a sort of mystical guide to the protagonist, often giving him tough love and urging him to keep on going when the chips are down.
The AMC adaptation -- while still supernatural -- is a little more grounded in tone than the comics, so it hasn't beer clear if Wayne would ever make an appearance as Jesse's imaginary friend. But in tonight's episode, "He's Gone," the prospect at least gets hinted at. When Tulip describes Jesse's gritty, often stubborn Texas character to Cassidy, she name-checks Wayne as his favorite actor. Who knows if her statement is prophetic or just a subtle nod to comic fans, but the possibility of eventually seeing Spirit-Wayne seems at least a little bit more likely now.