It's New Years Eve in New York City and Claire (HILARY SWANK) is the new Vice President of the Times Square Alliance, and her job today is to make sure the giant ball drops on schedule at midnight. With the aid of police officer Brendan (CHRIS "LUDACRIS" BRIDGES) she seems to have things in control, but when the ball ends up stuck during testing, she hopes they can convince former maintenance wizard Kominsky (HECTOR ELIZONDO) to show up and fix things.
She's also hired rock star Jensen (JON BON JOVI) to perform at the festivities, but he's preoccupied with the fact that he formerly proposed to caterer Laura (KATHERINE HEIGL) but then got cold feet. While she isn't happy to see him, her eager and sultry sous chef, Ava (SOFIA VERGARA), certainly is. Another woman, Elise (LEA MICHELE), also wants to see Jensen, but that's because she's one of his new backup singers. Unfortunately for her, she's stuck in a stopped elevator with comic book artist Randy (ASHTON KUTCHER) who doesn't like anything about New Year's Eve.
On the other hand, his best friend and courier, Paul (ZAC EFRON), is far more upbeat, and he gets an offer that might make his night outstanding. Record label employee Ingrid (MICHELLE PFEIFFER) has her hands on tickets to a big party, and she says she'll give them to him in exchange for helping her fulfill a number of potentially challenging resolutions she wants to make come true.
Sam (JOSH DUHAMEL) is also desirous of getting to that party, but after a minor car wreck, he must hitch a ride with a family headed to Times Square in their RV. As they travel along, he wonders if the stranger he met one year ago will show up as promised. Speaking of showing up, Griffin (SETH MEYERS) and Tess (JESSICA BIEL) are hoping that their baby will arrive right around midnight, so they can collect a prize of $25,000 if their child is the first born in the new year. They must contend, however, with James (TIL SCHWEIGER) and his pregnant wife who are desirous of the same thing.
Kim (SARAH JESSICA PARKER) doesn't have any newborns at home, but she does have 15-year-old daughter Hailey (ABIGAIL BRESLIN) who desperately wants to head into the city in order to be with the boy, Seth (JAKE T. AUSTIN) she likes. Her mom, though, doesn't think that's a good idea, much like a doctor (CARY ELWES) doesn't think his terminally ill cancer patient, Stan (ROBERT DE NIRO), she be allowed up on the hospital roof for one last view of the ball dropping. As a result, his nurse, Aimee (HALLE BERRY), stays close by to make sure Stan's last hours are as comfortable as possible.
As the hours count down toward midnight, all of those people try to resolve their various issues.