I assume I haven't missed anything. Flights between Prague and Florence are pricey as far as I can find on Lufthansa, Alitalia, etc. It will be my husband, myself and our almost 2 year old son so we want to reduce the amount of hassle in any way. Easyjet goes from Prague to Milan and then we could take the EuroStar to Florence to meet up with my family. Is that our best, most efficient bet?

You can check for less expensive airlines that may connect the two at whichbudget.com.

Another possibility is to check for flights between Prague and Pisa (an hour from Florence) which is a larger airport and ay have more choices.

Check flights from Prague to Pisa, Bologna or other close airports within an hour train ride of Florence.
http://en.wikipedia.org/wiki/List_of_airports_in_Italy

I would also check to see if there are some smaller airports close to Prague that serve some of the budget airlines.

Can you tell us what dates you are planning to travel? And, have you checked skyscanner.net?

There aren't smaller airports near Prague that would help, unless you find something from Brno, but doubtful.

Thanks for the replies. I checked Pisa a while back but need to do that again. I didn't think of Bologna, that's a good call! Thanks kybourbon for that wiki link, that is helpful!

If DH's vacation request is approved at work, we're looking at getting from Prague to Florence on July 9.

Just an update if anyone is interested - AirOne flies from Prague to Pisa for about 110 euros including fees. That may be the ticket! Thanks again for all the help.