A:Answer You can hold it in either hand (I just tried it right now), and it doesn't feel awkward, although the side buttons will remain on the left side of the mouse, instead of where your thumb would be. Also, the Primary and Secondary mouse buttons (left and right click) would stay where they are, unless you use the Logitech software to remap and swap left and right click.
TL;DR
It doesn't feel awkward, but buttons and layout isn't specifically designed for left-handed people.