I know Griffin covered some of the story in his great write-up of the game back at E3, but allow me to elaborate: Fawful has been going around the Mushroom Kingdom feeding Blorb mushrooms to the Toads, which cause them to turn into that big boulder from the Indiana Jones movie. It soon becomes an epidemic and Mario and Luigi are brought in to solve the case. But, Bowser intervenes and is summarily dispatched by the mustachioed heroes, only to be tricked into eating a different type of mushroom by Fawful afterward. He then goes back to the castle, inhales the duo into his body, and learns that he got duped. So while Bowser is trekking back to his castle to save it from doom, the plumbers are inside of their arch-nemesis, trying to find their way out.
Then there's the combat, which has a new layer of depth courtesy of the addition of Bowser. He's the big bruiser who can annihilate almost anything with a single punch, but when that doesn't work, he can suck enemies into himself and let the Bros. use their more robust move set to excel where their nemesis could not. Switching between Bowser and the Bros. adds more strategy to the combat and kept it from becoming too monotonous or stale throughout the game -- that was an occasional speed bump in previous titles. I only wished there were more of this three-way combat in the game, because there are large chunks where I was only able to use the Bros. or Bowser alone.
AlphaDream's writing and humor in these games have always felt almost timeless and the humor here, while definitely G-rated, is something that should work with gamers of all ages. And for those of you looking forward to the return of staple characters, know that Fawful is as endearing as he's always been (well, as endearing as a bad guy can be, anyway) and clumsy Luigi still gets no respect.
As hilarious as the game's story and characters are, though, they don't have to carry the experience alone. The combat, puzzles and witty dialog all come together to make a charming game that is AlphaDream at its consistent best. The series is still fun after all these years, and the new addition of Bowser really goes a long way towards freshening up the formula. Bowser's Inside Story is easily recommended to those of you who've played the previous games and is the best in the series so far.