The game starts with all players holding 16 cards. These cards have 0-4 microbes drawn on them (Sun, Moon, Mountain, Cloud). Once the game starts, the players may look at any and all of the cards in their hands. The game begins when the starting player places a card face up in the middle. The fastest player to find a card in their hand that either has one more microbe or one less microbe than the card in the middle and shouts out the name of the microbe that appears or disappears may play their card next. When a player places a new card in the middle, the other players must now search for a card that matches the above criteria for the newest top card.

If a player places the wrong card in the middle or says the wrong microbe name, shout "ZOGEN!" to call them out. The player that made a mistake will receive a penalty. However! Making a mistake is no problem as long as the other players don't shout Zogen. If a player can't find the correct card to play, they may choose to play the wrong card intentionally.

Play continues this way until a player only has 3 cards remaining in their hand. This player is the winner. Ranking is decided by how many cards remain in hand. The rules are very simple, but your head may start to spin as new cards are quickly played on top of others. Players may also decide to give the microbes new names. Please think of some funny names and give it a try!