Maybe it is just me but it has happened ever since I started using 0.6.x...
Every time I upgrade to the newest version, upon running the program for the first time, it looks like the icons along the top are not active. Just happened to me again when I installed 0.6.3
I installed Calibre, ran it, and oops! the icons do not work. I have to either quit and restart the program (works great after that) or I have to right click on a book and select an action from the pop up menu... after that calibre work fine.