Munchkins isn't a game with a great deal of depth. Thus, it behoves you as the gamemaster to encourage fast, funny play. If at any time nobody's engaged in shouted arguments over the significance of Courtney Thorne-Smith's black undies, getting chased by a cat, trying unsuccesfully to ride the family parakeet, or trying to shove an iron onto the head of the local toddler, then your players are probably contemplating how stupid the game really is. And that's never any fun.

So keep things moving. The game is generally at its best when the players are proactively getting involved in stupid schemes, but excitement level has to be quite high before they'll start entertaining themselves. You may wish to keep a list of diversions to throw at the players whenever action slows.

If you do come to a part where the game requires a period of extended inaction (for example, the Munchkins are all hiding in a closet), resolve anything necessary to be resolved with a few quick die rolls and get on with the game. The broad simplicity of the system should be used to make sure that the pacing never falters.

Content

I hate getting email from clueless morons who are pissed off at me because you offended them. So I'll keep this short, but sweet. Some elements of Munchkins are intended for those who don't mind sick, gross-out humor. Consider your audience. If they don't want to be subjected to such humor, don't force it on them.

I really shouldn't have to tell anyone this.

Remember that the simplicity of the system can be a drawback as well. Running an extended combat in the Munchkins system is a great way to get to sleep at nights. So all rolls should happen quickly and be subsumed into the narrative. If the Munchkins are battling rats, describe how the rats manuever around and menace the Munchkins, and only occaisionally call for an attack and damage roll. If you're using lots of exclamation points, you're probably on the right track.

Types of Games

There are basically only two things that Munchkins do -- they either try to drive off the Humans or watch and follow the commands of the Glowy Box. Both of these central features should probably fit into any Munchkins game, but you may wish to bias your game towards one side or another.

If your players are good at bickering amongst themselves and improvising, just show them some TV and let them go -- they should find plenty to entertain themselves with. However, if your players are more oriented towards traditional RPG activities of working towards a specific goal, you may wish to bias the game more towards plotting against the humans or pets.

It should be emphasized that Munchkins are highly helpless little critters, so getting rid of Humans will be quite a tall order. It may be better to use a pet or a child as the main antagonist.

Adventure Seeds

Here are some random ideas for how to start a nice one-shot Munchkins game:

Turn on the Great Glowy Box: The humans haven't turned on the GGB for weeks. You're dying, here. Somehow, you'll have to scale the smooth cabinet and get to the on-off switch (or, if you're particularly bright, figure out the remote control), and get some quality time in on the sofa. This is complicated by the family pussycat sleeping on the coffee table.
Aftermath of the Party: Last night was terrible -- seemingly endless numbers of humans invading the house, being loud, and getting in your way. And the Glowy Box was off. But now... Well, the giants are slumbering on the floor, making any kind of movement a constant danger, but the untold riches of junk food and beeeeeeeeeeeeeer await.
Pest Control: The humans were gone in the morning, and out the windows all you can see are strangely striped colors. Then the poison gas starts to filter into the house. Can you get out before you die horribly? We're betting you can't.
Pest Control mk II (Warning: This scenario is particularly tasteless.): One of the humans had been getting fatter and fatter, but then she got skinny again, and now there's another one! This is intolerable! Kill it before it grows!
Turf War: Rats are poaching your space! Drive 'em off.
In Other News: There are a whole bunch of humans next door, with lights and mysterious machines. And… Wait! The Great Glowy Box is showing the next-door house, too! What can it mean? Is there something there that both the GGB and the evil humans are trying to get?
The Great Outdoors: You did it. You drove out the humans. There was a week of beautiful uninterrupted time on the sofa. But then the Power went out, and all your sacrifices were in vain -- the GGB was silent. Then the wrecking ball came through the wall. There's only one solution now -- you have to strike off to find a new home, with a new, hopefully more talkative GGB.