Beth (Creator/KristenBell), a successful, single and clumsy woman, has been waiting for Mr Right for years but love is a luxury she can't afford and she's been left extremely bitter. She flies to Rome for her younger sister's impulsive wedding and meets Nicholas, a lovely yet equally clumsy man, and they hit it off. Just as Beth decides to get romance another go she sees him kissing another woman, the groom's "crazy cousin".

Drunk and angry, Beth picks up coins from the "fountain of love" and later learns from her sister, Joan, that legend says if you pick up another person's coin from the fountain that person will fall in love with you. The legend is true.

She is followed back to New York by a band of would-be lovers who have all fallen in love with her due to the spell. They are: Al, a sausage maker (Creator/DannyDeVito), a street illusionist named Lance (Jon Heder), a doting painter named Antonio (Will Arnett), and a narcissistic male model Gale (Creator/DaxShepard). She also meets up with Nick again and slowly falls for him, only to realise that one of the coins (a poker chip) belongs to him.

There are two ways to break the spell: return the coins to the owners or to the fountain.

!!Tropes:
* ActorAllusion: Once again, [[Film/NapoleonDynamite Jon Heder and Efren Ramirez]] are a team.
* BigDamnKiss
* CarMeetsHouse: Beth and her suitors driving their tiny car into the museum, the doors open and they knock over nothing before driving into the elevator.
* CastingGag: Having Dax Sheppard at a Kristen Bell's wedding when he's not the groom? Hilarious!
* ChekhovsLecture: "You cleaned me out last night, Padre"
* DancePartyEnding
* FakeNationality: In-movie example. [[spoiler:Although Antonio looks and acts Italian throughout the picture, when his coin is returned, he reveals that he is actually from Hoboken, having thought that going to Italy would make him a painter.]]
* TheKlutz: Beth and Nick.
* HeldGaze: Nick and Beth share two extremely passionate {{Held Gaze}}s, one right after they meet and one that ultimately leads to a BigDamnKiss while at the museum.
* HotForPreacher: [[spoiler:Inverted, the poker chip was the priest's]].
* MisplacedNamesPoster: [[http://inhearitplay.files.wordpress.com/2010/03/when-in-rome-poster.jpg That's]] not Kristen Bell, that's Josh Duhamel! That's not Josh Duhamel, that's Kristen Bell!
* NiceJobBreakingItHero: More like nice job Not breaking it.
* OohMeAccentsSlipping: Once the spell is lifted, Antonio is revealed to be an American named Tony.
* PairTheSpares: Tony and Gale seem to get together; Celeste and Al definitely do.
* SelfProclaimedLoveInterest
* StalkerWithACrush: All of the men who are after Beth.
* UnwantedHarem: Of men