Until 2008, thrillseekers took their life in their hands dashing across Strip traffic to get near the sign, but now there's a parking lot in the median so you can pull over to grab the money shot. The only entrance is on the southbound lanes of Las Vegas, a little ways south of Russell Road. You can try to find a slack time to strike your pose, but otherwise you'll wait in a long line to get on the grassy knoll beneath the sign, because in addition to the carloads of shutterbugs, tour buses stop here regularly with a load of passengers. Others are content to stand off to one side and grab their pictures and/or selfies from a respectful distance.
If you want to be at a really respectful distance, there's always the replica sign on Boulder Highway, although unless you snap a shot as you drive by, you really would be taking your life in your hands trying to run up to it.