The Knife is a starting weapon that the player begins the game with, along with a handgun. It appears in many Resident Evil games as a extremely weak weapon used when the player wants to save ammo or use it as a last ditch effort to kill a Zombie if the player has no ammo remaining.
In Resident Evil: Code Veronica, the knife would see a boost to its efficiency. Properly timed swipes at enemy zombie's legs could result in causing the zombie to collapse to the ground, buying either Chris or Claire Redfield time to either use their handgun on a less mobile enemy, or continue to stab at them. Additionally, properly placed swipes of the knife could result in multiple strikes on an enemy in a single attack, allowing for the possibility of killing zombies before they can get back to their feet.
In Resident Evil 4, it is powered up and is used commonly throughout the game. Through normal gameplay it is used against Ganado, as well as to break open boxes that may contain useful items. The knife used in major battles such a the El Gigante fights, the cutscene fight with Krauser, and the final encounter with Saddler. These traits are suspected to be similar in Resident Evil 5.