When would local caching work for a global user base?

I'm on a project with a fast-growing global user base and we're seeing some performance issues. We use local caching a lot for data people access often. It's been okay, but I'm thinking this might not work much longer because of delays for users far from our main data centers. So, when does local caching, even with a CDN for static stuff, just not cut it for a worldwide audience? What kind of numbers or signs tell you it's time to stop relying on just local cache?