Working with Shapekeys in Blender

When working with Shapekeys in Blender, it can be relatively easy to accidentally break things.

Make sure to always be mindful of which shapekey is actively selected before manipulating anything in edit mode.
Merging vertices can result in awkward behavior. Make sure to turn off auto-merge when manipulating any mesh with shapekeys, as it can be easy to accidently merge some vertices and ruin existing shapekeys, including the basis.
Modifiers are not normally appliable once a mesh has shapekeys. Try to apply any modifiers before beginning the shapekey process. As with any one-time, destructive operation in Blender such as applying an object modifier, it can be a good idea to store a backup copy of the file just in case you ever need to undo. You may still want to keep the mirror modifier enabled, and instead use some other tricks or addons, such as the ones listed below.

I use this one personally.
SAVE before using this tool, as it is crash prone.
If any errors occur, it’ll post to the Blender Console.
- A typical error is a vertex count mismatch, typically caused by vertices being merged by the mirror-modifier in some Shapekeys but not others. Find the problem Shapekey, which might be listed in the error message. If it is not listed, walk through your Shapekeys and monitor your object’s vertex count. If it goes down or up, you’ll be able to know which shapekeys need to be fixed. Moving them away from the symmetry line in the mirror modifier should fix things, or adjusting/disabling the mirror modifier’s Merge Distance parameter.