ZBrush has two major modes, a 2D paint mode that operates on the canvas, and a 3D Edit mode that operates on 3D models. These modes complement one another and can interact with one another, but they are quite distinct. In addition, each mode can have one of various sub-modes active. The complete set of mode controls can be found above the canvas area:
These buttons can also be found in the Transform palette.
Which of the 2D paint or 3D edit modes is active depends on whether or not the 3D Edit button is active. When it is active, ZBrush is in 3D Edit (modeling) mode, and when it is inactive, ZBrush is in 2D Paint mode. The hotkey for switching between modes is T.