there's a ton of ways to do it...weld a strip of metal in there, sand it down, and use body filler, fill the majority of the gap with fiberglass and then bondo over top, fill the whole thing with bondo, fill it with dog poo....choose your way of doing it.
I'm probably gonna be going this route because I don't like the idea of water sitting behind my mouldings and rusting out my door skins. I'm unsure of the method I'll be using, depends on how much time/money I decide to put into it, or who I end up having do it.