As each level starts there are a number of holes (visualized as huts) in the teeth you must protect, from which bacteria emerge. The bacteria go through several stages that get progressively harder to kill, but in the first stage they are able to multiply and so the problem gets rapidly out of hand. Closing these holes and stemming the flow of new enemies is therefore the first order of business. Once you've used your toothbrush to dispatch these cavities, you must hunt down the remaining bacteria, using shots of toothpaste to kill them.
Along the way you can pick up power-ups that will replenish your health, ammo or give you double damage.