The Resident Evil franchise has introduced a plethora of challenging bosses that have tested players' skills over the years. This article ranks the 15 most difficult bosses, starting with Nosferatu from Resident Evil: Code Veronica, a creation of Alexander Ashford that is intimidating due to its lack of cover and limited resources. Mr. X from Resident Evil 2 is another memorable adversary, known for being nearly indestructible and requiring players to evade rather than confront him. Marguerite Baker from Resident Evil 7 stands out for her grotesque appearance and the draining nature of her battle. Victor Gideon from Resident Evil Requiem challenges players to master the game's mechanics, particularly on higher difficulty levels. Lastly, Albert Wesker in Resident Evil 5 presents a significant challenge due to the need for precision in a lava-filled environment. Each of these bosses not only provides a tough challenge but also enhances the overall experience of the game.