You place new atoms onto the circles on the board, optionally rotating them to fit first. Atoms cannot be rotated once they are placed. Choose the position and orientation of atoms carefully, or you will paint yourself into a corner. Green circles are places where the current atom can be placed. Yellow circles are places where the current atom might be placed if it were rotated. Red circles are places where the current atom cannot be placed no matter how you rotate it. You may rotate either by dropping an atom onto a rotation button, or by pressing the left and right arrow keys on the keyboard.

Helium(He) and the Mystery Element(?) are special atoms. When a Helium is placed, it will immediately disappear, taking along with it any adjacent atoms. When the Mystery Element is placed, it will change into whatever atom will fit there, depending on how many bonds are adjacent. If there are no adjacent bonds, it will turn into a Helium, and behave just like a Helium would.

Chemical Q is also a special atom, as you are never given one during the course of a game. The only way to make Chemical Q is to use a Mystery atom on a space that connects to six bonds.