Let the Pencil toggle. Because the Pencil erases its own colour, you can fix single-pixel mistakes by clicking them again—no tool switch.
Keep a 1× preview open. A floating preview window Option+Command+P shows how the sprite actually reads while you work zoomed in.
Sketch loose, ink clean. Rough out shapes with a large brush on one layer, then draw clean 1-pixel lines on a layer above with Pixel Perfect F on. Delete the sketch layer when done.
Flip to find errors. Flip Canvas Horizontally Shift+H—lopsided artwork jumps out immediately in the mirrored view. Flip back when you’ve seen enough.
Half a face is enough. For anything symmetrical, turn on Tools > Symmetry and only draw one side.
Fewer colours, better art. Small palettes force stronger shapes and contrast. Start with 4 colours and add only when something can’t be expressed.
Build ramps, then use Colour Shift. Lay your palette out as consecutive light-to-dark ramps and the Colour Shift brush becomes a one-stroke shading tool.
Dither against transparency. Set the secondary colour to the eraser and use a mid dither level for soft, airbrushed-looking erasing.
Recolour a layer in one click. Fill with Control held replaces every pixel of a colour on the layer, connected or not.
Protect what matters. Mark transparency or key colours as protected so no stray stroke can touch them.
Share a background across frames. Draw it once, then Layer > Duplicate Layer to All Below stamps it onto every frame.
Use Toggle Zoom. Z flicks between fit-to-window and your detail zoom—faster than zooming in and out manually.
Name sheets for round-tripping. Keep the -table-16-16 suffix on exported sheets and they reopen frame-per-layer.
Nudge with intent. Arrows move a selection 1 px, Shift+arrows 10 px; Shift+arrows nudge the layer when nothing is selected.
Let presets do the period-accuracy. The Famicom/Atari ST/Mega Drive presets set the right canvas, palette, and pixel shape in one step.