While I'm a huge fan of Smart Folders in Mail, I've possibly been abusing them and not filing my mail at all. Once I had around 10,000 messages in my inbox, I decided that it was time to do something about it. Ideally, I'd have multiple sub-folders, such as Clients and Vendors, and then in these folders, I'd have Client Name A, Client Name B... and Vendor Name A, Vendor Name B, etc.