I use these > http://www.amazon.com/INCRA-Build-It-Hold-Down-Clamp/dp/B000W07PEM (x10) and these Kreg KMS7511 - Trak Clamp | Woodcraft (x8)
After I load the gcode and touch off X & Y. I jog the machine around the outer perimeter of the live view of the toolpath to make sure the hold downs are not in the way. If I am going to to be doing edge-to-edge work, I first make a four holes in the four corners of the material and place 4 metal dowel pins in the holes and line them up to the pre-made holes in my wasteboard. (This is great for full duplex ops)
Once you get into your standard workflow/routine on hold downs, and make a small check list before you press the ‘Go’ button- Your errors will go down dramatically.