The slim plot revolves around Wario's attempt to break into the games industry, after realising he can make a quick buck like everybody else currently in the business (Wario is some evil relation of Mario, I think). The player's duty is to defeat Wario by beating his games. And there's a lot of them. 213, in fact. They only have one thing in common: they last five seconds. You can be picking a persons nose, racing in F-Zero, cutting steak, jumping sharks, saving penalties, and fighting WWI planes all in the space of thirty seconds. It's completely insane.
The game is broken up into several different stages, each of which have their own peculiarities; one will chide you for not having bought a Gameboy Advance SP yet, while another is set inside a toilet. Completion of a stage will allow you to play the games you have unlocked at any time, and may also reveal hidden features such as two-player activities or extended versions of particular mini-games. You probably won't unlock all 213 games when you first complete the main game, and The Grid will taunt you by showing a series of question marks. You will play, and play, until all those marks have been removed.
Your life will soon devolve into a series of simple verbs:
It commands you. A quickly barked order. A reaction test game. Then another. Then another. And another. You die. You reach the BOSS STAGE! You start again. Jump! Catch! Bounce! It's the greatest video game since, well, Tetris.