I just went through this, and it took a little fiddling, so I'll try to describe what has worked for me.
I have a Garmin eTrex Vista and a Mac iBook G3 running OSX 10.4.10. I bought a USB-serial adapter from Radio Shack and use it together with the cable that came with the GPSr.
I downloaded the programs MacSimpleGPS and gpx2ipod.
http://www.macsimplegps.com
http://www.birdhouse.org/software/gpx2ipod/
MacSimpleGPS sends/receives .gpx and .loc files to/from the GPSr. Here's the detail that I had to figure out for myself: After you connect the GPSr and launch MacSimpleGPS, go to MacSimpleGPS>Preferences...>GPS Unit and select Port PL2303-181 or some number like that, not the modem port. After that I had no trouble. Also, make sure that on your GPSr, under Main Menu>Setup>Interface, you choose Serial Data Format=GARMIN. None of the other data formats worked for me.
gpx2ipod is pretty simple; it converts .gpx files to a Notes file on your iPod. The main thing is to "Enable Disk Use" on the page where you set the preferences for your iPod. If you don't have an iPod, there are programs that do the same thing for a PDA like Palm. I just didn't want to have another device that I had to connect to my laptop.
So my usual routine is to take the unzipped .gpx files that Groundspeak sends, open them with MacSimpleGPS, and then after I upload the waypoints to the GPSr, I drag the .gpx files to the Input folder of the gpx2ipod folder. After that program does its thing, it moves the .gpx files to an archive folder.
Trust me, after you get this working, you will never go back. It is a revolution, and you'll be doing Pocket Queries all the time. My only problem is that the Vista has room for 500 waypoints; jeez, a pocket query can send 500 waypoints all at once!
Good luck. Let me know how it goes.