Can you regenerate a creature after it has been dealt lethal damage?

Regeneration works as a replacement effect that replaces the event of a creature being destroyed. When a creature has been dealt lethal damage, it is marked for destruction, but that destruction hasn't happened yet — state-based actions are checked and applied at specific times (such as before a player would receive priority). This gives you a window to activate a regeneration ability in response to damage being dealt, or even after damage is on the stack resolving, as long as the creature hasn't yet been destroyed by state-based actions.

According to CR 701.15a, to regenerate a permanent means to create a replacement effect that replaces the next time that permanent would be destroyed. When destruction would occur, instead the creature is tapped, all damage is removed from it, and it's removed from combat (CR 701.15b). Crucially, state-based actions (CR 704.5g) — which destroy creatures with lethal damage — are only checked at specific points, not continuously mid-spell or mid-ability resolution.

So after damage resolves, you still have the chance to activate a regeneration ability (like that on Drudge Skeletons) before state-based actions are applied. Once you activate it, a regeneration shield is set up, and when the game checks state-based actions and would destroy your creature due to lethal damage, the shield intercepts that destruction.

Example: Your opponent casts Lightning Bolt, dealing 3 damage to your 2/2 Drudge Skeletons. Before anyone receives priority after the Bolt resolves (but before state-based actions destroy it), you activate Skeletons' regeneration ability. When state-based actions are checked, the lethal damage would destroy the Skeletons, but the regeneration shield replaces that destruction — the Skeletons survive, tapped, with damage removed.

Note: Regeneration does NOT work against effects that exile a creature, destroy it with an effect that says "can't be regenerated" (like Wrath of God), or sacrifice effects — those don't use the destroy mechanism that regeneration replaces (CR 701.15c).