Just like the description states, kill three enemies with a single shot. It must be with the bullet, and cannot be with an exploding barrel. As you progress through the game, more and more enemies fill the levels. This will require a bit of luck to get three to line up. It also helps if you use some Reactix pills to slow down time to help you better time your shot. Just be patient. If there is a lot of enemies, and you are in a position on the ground, three will line up...just wait for that shot. There will be many instances where 5 or more enemies line up.