Well, this can pretty much serve as the canonical example of "high concept" comedy. In an alternate world, humans never developed the capacity to lie. Don't think about that too hard. Enjoy the little throw-away jokes, like how advertising works in this world ("Coke. We're very famous." or "Pepsi. For when they don't have Coke.") Don't question how advertising would even exist in a world without lies.
In such a world it sucks to be short and pudgy with a snub nose, like Mark Bellison (Ricky Gervais). Everyone tells him what they really think--that he looks like (and therefore is) a loser. After the girl of his dreams (Jennifer Garner) rejects him, his boss fires him, and his landlord evicts him, he goes to the bank to withdraw his last $300 so he can start his new life as a homeless man. The system is down, so the teller just asks him how much is in his account. And something in his brain snaps. Instead of telling the truth, he says there's $800--just enough to pay his rent. And it works.
He uses his new super power to get a lot of money, (almost) have sex with a strange woman, and even start a religion. That starts with him trying to comfort his dying mom, and leads to him presenting his version of the 10 commandments on pizza boxes. But it's a surprisingly kind comedy. Mark is fundamentally a nice guy (probably comes from being kicked around so much, he can empathize with the miserable losers), and he doesn't take full advantage of his power. While he makes life nice for himself (mansion, fame, etc.) he simply doesn't have the killer instinct to use it to hurt anyone else. And in the end, the movie makes the case that a judicious amount of lying is good for the world.
It's a ridiculous concept that shouldn't work, stretched way too thin, and completely toothless. But the comedy works because of a very talented cast. Besides Gervais, Rob Lowe stars as his nemesis, Louis C. K as his best friend, and cameos by Tina Fey, Philip Seymour Hoffman, Jonah Hill, Jeffrey Tambor, John Hodgman, and others. Enjoy their performances, just don't think about the concept for more than a few minutes, or it will collapse.