My wife and I used the Student Bus service to get from Cesky Krumlov to Prague. Rick Steves' Prague and the Czech Republic book said on page 231 that '2 of the daily departures - 12:00 and 16:45 - can be reserved and paid for at the TI'. We asked at the TI and they are now able to book all Student Bus departures (we were in Cesky Krumlov in late September 2014). When we boarded the bus they did have a list and did check us off, but others were able to buy tickets from the driver and hostess, although I would expect this conditional on space being available.
The ride was comfortable, and even with a few stops to pickup additional passengers, we were in Prague in 3 hours and 5 minutes.
As the book says the bus depot in Prague is at Na Knizeci, which is true. This is on the west side of the river, south of the Little Quarter. It is not the main bus station, but it is right at the Andel Metro stop on Yellow Line B so it is easy to get to your hotel as long as it is close to a Metro stop.