Invasion of the internet - (aka Crossing State Lines)

I have recently been approached by a few friends looking to starting new internet-based businesses. One will be selling advertising, the other an information management services. Though nothing physical will be sold, they do hope to eventually have clients and sales across the country. Since I predominantly handle individuals with small, local businesses, I have a lot of catching up to do on multi-state tax issues before I feel ready to consider handling this. At what point would it become a multi-state tax issue? Is it when the out-of-state company buys advertising from my client?
Does anyone with internet based clients want to share some war stories?

Marci