Yes, yes, Askimet is awesome, but add WP Hascash plugin and you'll take it to another level, it stops the bots before they even have a chance to enter a spammy comment.
WP Hashcash is an antispam plugin that eradicates comment spam on WordPress blogs. It works because your visitors must use obfuscated javascript to submit a proof-of-work that indicates they opened your website in a web browser, not a robot. If the javascript check fails, WP Hashcash now gives you three options; it can either put the comment into moderation (default), put the comment in the akismet queue, or delete it.
http://wordpress.org/extend/plugins/wp-hashcash/