Welcome to a wonderful new world. What type of machine do you have?

Many people use proximity switches (which I thought came standard with new machines?) to "zero" the X and Y axes. Once you get them set (use the Tools/Setup command with the tool located exactly at your 0,0 point) they are pretty reliable.

Some Shopbotters have mounted laser crosshairs on their gantry to help with manually locating the corner of the workpiece. Search the forum for 'laser' or 'laser pointer' or something similar.

Another technique is to screw a couple of pieces of plywood down in an "L" shape, and use the machine to trim one edge of each piece, to create accurate reference surfaces to register the part against.

It can often be helpful if you can make the blank oversized so you can concentrate on other issues and not have to worry so much about the registration - although that's not always possible.

Good luck with your new machine!