Renting a Van/Car with US Drivers License

Is there any hassle in renting a van (for moving) or a car (in general) while having only a US Drivers License.   I'm sure for cars/tourism it must be pretty common, but how about for the companies that dont deal with tourists much, but more like those who rent vans to use for small moves.  Has any body done that, should there be any issues there?
Just wondering and hoping it should be an issue.  I know eventually we have to get a UK Drivers License if we intend to drive here, but not sure on the rules etc...
Thanks!

Shouldn't be a hassle but you won't know unless you try, really. 

I've rented a car three different times, mostly for weekend moving, without any problem whatsoever. Enterprise has had the best prices each time for the smaller vehicles.