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I use it for closing tabs in Firefox when I don't have two hands on the keyboard (W is on the right hand's side of the keyboard for us Dvorak folks).

A middle click anywhere on the entire tab is easier that hitting the lil' x button. Plus, you can turn off the 'close tab' button it the options and make your Firefox look a little bit cleaner.

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If you don't have a middle-click, how do you open a link in a new tab? (honest question, I buy mice for this.)

If you use OS X, cmd+click.

Cmd+click even works on some things that middle click doesn't, for example middle clicking on the home, back/forward, or top sites buttons in Safari will do nothing at all, but cmd+clicking will properly open your home page, previous page, or top sites page in a new tab.

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