I play a right handed ukulele left handed (neck in my right hand, strumming with the left hand, but strung normally). Since the body is symmetrical, and I learnt like that from the start, I've not really had an issue. Plus, it means I can pick up and play any old ukulele without having to re-string it first. However this doesn't work for something like an electric guitar which you cant really play "upside down"