Frankfurt is notorious for room shortages during busy trade fairs. If you have the bad luck to arrive when one of them is scheduled, you may find all the more central hotels fully booked. To find an available room, head to one of the tourist offices or book online at www.frankfurt-tourismus.de.
Even without the fairs, Frankfurt is one of the world's great commercial hubs, so businesspeople pour into the city at all times of the year. Hotels, for the most part, are expensive. However, you can sometimes negotiate a rate decrease on weekends when the business clients don't predominate. Hotels also tend to be booked well in advance, so reservations are important.
Nearly all the major hotels in the city center are convenient to the train station, the business district, and the fairgrounds. Of course, you can take a taxi, but walking time is often no more than 20 minutes to where you're going.