Orphaned siblings Andi (Emma Roberts) and Bruce (Jake T. Austin), have been forced to hide their ownership of their beloved dog, Friday, as they move from one foster home to another. They deceive a pawn shop to get money for hamburgers for themselves and the dog, but are caught. Their social worker Bernie (Don Cheadle) reprimands them, but helps them to minimize the damage.
They secretly turn a closed hotel into a home for Friday and any other strays they can find. They are joined by a guy named Dave (Johnny Simmons) and a girl named Heather (Kyla Pratt), both of whom work at a pet store; Dave and Andi soon develop crushes on one another. They are later joined by a kid who lives nearby named Mark (Troy Gentile), who likes Heather, although she does not return the feelings.
The kids rescue many dogs, and Bruce invents and constructs many ingenious machines, using parts he steals from his foster parents, to help feed the dogs and provide sanitary facilities, exercise and entertainment to them. The dogs are quick in learning how to use the machines.
Bernie is pleased to tell them they can move from the foster home they hate to a new one that is a few hours away. Even though this may be their last chance to be placed in a foster home together, they decline as they care too much about the dogs to abandon them, but they cannot tell Bernie this reason because they might be forbidden to continue their care for the dogs.
One night while Andi and Dave are at a party, the machines fail and the dogs go wild and cause so much noise that the cops are called. The dogs are taken to a pound and Bruce and Andi's foster parents kick them out for stealing, and as predicted they are sent to separate foster homes. The pound prepares to put the dogs down, but Friday escapes and gets to Dave.
The two reunite all of the kids and they decide to save the dogs despite the fact that they are going to get in big trouble. They break the dogs out of the pound and try to lead them over the county line to an animal shelter there that has a no kill policy, but as the dogs get close to the hotel, they turn and run there as that is their home. The kids and a massive crowd of people follow. At first, Animal Control tries to take them back, but Bernie, having seen what the kids did, makes a speech in favor of the dogs as the kids rescued so many strays and gave them a home, something he had been trying to do with the kids he dealt with.
With donations from the people of the city the hotel ends up fixed up and turned into an actual hotel for dogs named The Hotel For Dogs. The kids all work there, Andi and Dave kiss,and Mark starts to win Heather over. Bernie and his wife end up adopting Andi and Bruce and let them keep "Friday".
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