While the car driver is still unknown, he/she played a major role in the episode "Life of Brian" by killing Brian in the process of running him over with the car, continuing to drive after having done so. Nothing more is known of the driver, though they reappear in the episode "Christmas Guy" where Stewie travels back to before the driver killed Brian and saves him.
"Life of Brian"
In "Life of Brian", After Stewie and Brian travel back to the 17th century in Stewie's time machine and give the Indians guns, they travel back to fix their mistake. Later after Stewie realizes the dangers of time travel, he decides to take his time machine apart and never time travel again. After taking it apart, Stewie ask Brian to help him haul it off to the dump so he can crush it down and won't be able to put it back together. While at the dump, Stewie and Brian find a street hockey net and take home so they can play with it. While Brian sets up the net, an unknown assassin rounds about the corner in a car and runs Brian over, killing him, and ruining the net, Brian's death hits the whole family hard and they bury him.
Two episodes later in "Christmas Guy", While Stewie was sitting on Santa's lap at the Quahog Christmas Carnival, Santa asks Stewie what he wants for Christmas. After thinking for a while, Stewie realizes that he wants Brian back. Stewie is sad without Brian and doesn't know how to bring him back. However while at the mall, he discovers a past version of himself with the old return pad of his time machine. He soon recalls a cutaway gag in Life of Brian and remembers before Brian's death Stewie told him he travel ahead to Christmas to purchase a toy so he wouldn't have to wait for it. Stewie realizes that he can use it to travel back to before Brian was killed and save him. Once Stewie time travels back to before Brian died, he sees Brian on the road with the street hockey net and then see the car driver that originally ran him over round about the corner like before. And this time, Stewie pushes Brian out of the way of the car and saves him. However the net is still ruined. Stewie then tells Brian about how the car killed him, and that how he traveled back to save him and Brian thanks him for saving his life. Afterwards, Brian realizes Stewie is starting to fade away. Stewie tells Brain that now that he's saved him, the timeline that the car driver created with Brian's death no longer exists. Future Stewie then wishes Brian a Merry Christmas and disappears. Afterwards "Life of Brian" Stewie walks out and asks Brian "Hey who are you talking to out here?" to which Brian replies "A pretty awesome guy."
- So far, it is unclear who the driver is, and it likely will never be revealed. Several fans have theorized that it was probably any character who hates Brian, with Peter's friend Glenn Quagmire and Lois's father Carter Pewterschmidt being the most accurate prime suspects.
- Brian's death can be considered ironic because he was killed by a Prius, a car which he highly respects. He evens owns one. The model of the infamous car is actually a Mercedes-Benz E-Klasse.