NOTE: This spoiler was submitted by Jeremy.
The film opens with Dan Trunkman (Vince Vaughn) arguing with his boss Chuck Portnoy (Sienna Miller) of Dynamic Systems over Chuck giving Dan 5% less commission on a business deal. Dan calls Chuck out on her dealings and behavior, and then decides to leave and start his own business. Only two other people follow Dan - Tim McWinters (Tom Wilkinson), who claims he was just let go for being too old, and Mike Pancake (Dave Franco), a young man that just had an interview at Dynamic but is eager to join the other two.
A year later, Dan's business, Apex Select, has barely gotten off the ground. He, Tim, and Mike are sitting in a Dunkin Donuts when Dan gets a message to go on a business trip to Portland to meet with investors Jim Spinch (James Marsden) and Bill Whilmsley (Nick Frost), the latter being an old friend of Dan's.
At home, Dan's kids Paul (Britton Sear) and Bess (Ella Anderson) are being bullied at school. Paul is constantly ridiculed for his weight and penchant for wearing eye shadow. Bess asks Dan to finish a homework assignment of hers that requires her to describe the kind of person her dad is. Dan's wife Susan (June Diane Raphael) wants to put Paul in a private school despite the pricey tuition for the school they want to put him in.
The three head to Portland, only for Dan to discover that Chuck is there trying to close a deal as well. She gets on with Jim easily (it's implied they're sleeping together), and it appears as though she's got her business ready to go. Dan gives his presentation to Jim, only to faint in the middle of it. He makes Mike go up to finish, but everyone is distracted by Mike's last name. This forces Dan to scramble and find a way to get a step ahead of Chuck. Dan also starts to lose faith in the team since Tim is more concerned about finding a woman to sleep with since he's unhappily married, and Mike never finished college and is also possibly autistic.
Dan is told to go to Berlin to meet with another investor, Maarten Daaervk (Uwe Ochsenknecht). He travels with Tim and Mike and they go to find a client, Helen Harlmann (Bonita Friedericy), at a unisex bath house. He makes Tim and Mike wait outside out of fear that they'll blow the business opportunity. Dan finds Helen with three other people. She says she doesn't trust him since he walked in there fully dressed in a suit. Dan undresses himself and gets Helen to listen to him.
Mike finds a hostel for them to stay at. Dan is put in a room that is actually an exhibit where everyone watches him as he goes about his business, and he is dubbed "American Businessman 42". He starts to put some numbers together to outdo Chuck. Tim and Mike follow him to find Bill in a gay nightclub during an event. Dan encounters Bill in a bathroom with other men sticking their penises through glory holes. Bill explains this is the only way he can get any sort of pleasure. He takes a look at Dan's numbers and says they definitely trounce Chuck's numbers.
Dan learns from Susan that Paul got in trouble at school for wearing eyeliner, and Bess got in trouble for beating a kid that was making fun of Paul.
The guys find Jim and learn that Maarten Daaervk is in St. Louis, which is the guys' hometown. Dan is annoyed to learn they traveled all that way when he was going to be at home anyway. Jim also tells Dan that while his numbers are good, they aren't enough to close the deal.
Things take a turn for the better when Dan manages to score a meeting with Daaervk. But first, the guys must pass through a riot going on outside the building where they need to find Daaervk. After evading police and getting pelted with paintballs, the guys make it inside. Daaervk likes what he sees from Dan, and they close a deal, thereby saving Dan's business. He, Tim, and Mike celebrate by gloating in front of Chuck in her exhibit room (Mike even moons her), while they pass Jim, and Dan gloats to him as well.
The guys return home to their respective loved ones. Mike rejoins his friends from the special homes and boasts about getting laid in Berlin. Tim reunites with a maid he encountered in Portland. Dan rejoins his family, now confident of their future.
During the initial credits, Dan realizes he forgot to do Bess's homework. She tells him she did it herself. He reads it to find that she wrote, "My daddy is the person who drives when everyone else is tired." Dan smiles.