Jesse Custer met Skeeter at a gas station on his way to track down his girlfriend, Tulip. The dog seemed friendly enough - too friendly, perhaps. Skeeter tried to "play" with a visiting police officer, and got a kick for his troubles. When Custer confronted the officer, he ended up punching the man right through the windshield of his patrol car.
Skeeter and Custer were inseparable after that, and took a long journey around the country together. Skeeter was an intelligent dog, and helped save Custer's life several times. He also took to Custer's friends, making him a very well-liked part of the group.