The first thing I chose to tackle, for sheer numbers alone, was my Magic: The Gathering card collection. Since the only thing it was gathering was dust, I decided to box up my commons and uncommons (and some rares) in a giant flat-rate box.
One fixed-price auction on eBay and they were gone. Over 5,000 Magic cards and 26 pounds of dead weight out the door. I'm still selling off my rare cards piecemeal... but chances are those will be in a lot when I get tired of selling everything one at a time.
Click here for a guide to getting rid of your junk. I just watch Hoarders to get motivated, but some people like lists.
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