On each level, you'll see a colorful layout of bubbles arranged on a grid, and a selection of starter bubbles in a box on the left. To start a combo, drag a bubble from the box into an empty spot on the grid. It will pop, causing any nearby bubbles of the same color to pop as well, setting off a chain reaction. Your objective is to obliterate all the bubbles in the grid (except for the ones decorated with a skull-and-crossbones) without running out of starter bubbles.
As you beat levels you will, as the instructions say, "meet new and exciting balls that do different things and offer new challenges." Which means the further you get, the harder Popopopopop tries to make your life a living hell. What initially looks like a pure puzzle game pulls back its mask to reveal a gauntlet of precision timing and mouse dexterity.
Among the special bubbles are the needle, which gives you a limited amount of time to pop stray bubbles with your cursor directly; and the thundercloud, which can destroy all the bubbles in a straight line, but requires split-second timing to hit your target. Those Jolly Roger bubbles I mentioned, if popped, instantly make you lose. One bubble actually blacks out the screen and forces you to complete the level by intuition.
So it's not a nice game. There's even a level called "Blind Luck", and it ain't kidding. A lot of players will give up at that point, if they didn't already quit at "Perfect Timing" or "Perfect Timing II". But it's all in the spirit of fun. You can easily picture the makers of Popopopopopop giving each other high fives as they discover yet another way to cripple the poor suckers playing their game. "Hey, what if we blind them now?" "Yeah, and then let's cut off their legs!" "Yeah! Screw you, players! Hahaha!"
If the official levels are getting you down, give some of the player-created levels a try. As part of the current, welcome trend in web-based puzzle games, there's a simple level editor with a rating system. That alone makes Popopopopopopop more like a playground than a challenge. Good, silly, frustrating fun. Once you stop to pop, you can't stop the pop till you top the crop of pop pop pop pop.