It works like this: whenever a comment, trackback, or pingback is posted on your site, it's sent to the Akismet website, which tests it and sends back either a favorable or unfavorable result.
With Akismet, you don't need to keep a black list of spammers any longer. This web service takes care of everything.
If you happen to receive a false positive, you can always get in touch with Akismet to get a different result.
To use Akismet, you need an API key, which you can get on the user registration page on WordPress. Click here to access it.
Both the script and the API key are free, but you can get commercial keys with other useful features from the developer's website.