I'm doing R&D for my employer using Catalyst for AJAX applications right now. The key is the Javascript library you use. Remember - Ajax is just a way for the browser to make HTTP requests without having to refresh the page. Nothing less, nothing more. On the serverside, you're doing standard HTTP request/responses. You can use Catalyst, CGI::Application, Maypole, OpenInteract, or whatever else you want to use.

The JS side is where things get interesting. I personally use HTML::Prototype and the Prototype JavaScript library for my AJAX work. (I have documentation for this forthcoming.)