- Rex I (Two Dozen and One Greyhounds)
- Rover II
- Fido II
- Rex II
- Dave I
- Jay I
- Paul I
- Branford I
- Dave II
- Jay II
- Paul II
- Branford II
- Grumpy I
- Grumpy II
- The Puppy Formerly Known As Prince
They were born in the Simpsons kitchen in several hours and each had their own personalized bowl. They enjoyed ripping Bart's socks to pieces, until he had to resort to wearing Lisa's socks. They also enjoyed stealing potato chips out of Homer's hands before he could eat them. Marge made the family wear flea collars instead of the puppies since "it's just easier that way". They went to the bathroom on newspapers in the kitchen, and Homer just put new newspapers over the old ones, causing the house to stink.
The family decided to give the puppies away after they blew their second chance, getting Homer into trouble with an IRS officer, Homer's US Army drill inspector, and Reverend Lovejoy at a dinner party. The next day, Homer put up a sign that said "Puppies for free (or best offer)" and attempted to sell them to neighbors, but the puppies didn't like being split up. Mr. Burns offered to take all of them, but the family refused for obvious reasons. Then he kidnapped them right from under their noses.
They were taken to Burns Manor after being kidnapped. One of them stood up, which reminded him of Rory Calhoun, and he named it Little Monty. Bart and Lisa found out where the puppies where and discovered Mr. Burns giving them a bath. They thought that they might have been wrong about Burns, until they hear about his plan to make them into a tuxedo. Bart and Lisa attempted to rescue the puppies, but were stopped by Burns in the basement. He was about to kill the dogs, except for Little Monty, who stood up and Burns knew who not to shoot. Then, Bart used a clothesline with Burns's socks hanging from it to get all of the puppies to stand up. Mr. Burns was almost going to kill them all, but couldn't since they were too cute.
Once they became adults, the 25 puppies became world racing dogs champions, making Mr. Burns win over 10 million dollars.
Santa's Little Helper also had once more eight greyhound-poodle hybrid puppies, with Dr. Hibbert's dog, Rosa Barks. Dr. Hibbert left the puppies with the Simpsons, and they were their problem. Homer, took Santa's Little Helper to be neutered, but couldn't carry out the deed. They give the puppies away to townspeople, including Krusty, Willie, and Snake.
- Despite being only 25 puppies, there are actually 26 names.
- Cleo and Queenie appeared to be the only two female puppies.
- Episode – "Two Dozen and One Greyhounds" (First offspring)
- Episode – "All Singing, All Dancing"
- Episode – "Burns, Baby Burns" (mentioned)
- Episode – "Today, I Am a Clown" (Second offspring)
- Episode – "A Father's Watch" (couch gag)