Wordpress has a nifty feature for fighting comment spam. It allows you to blacklist certain words (like Viagra, casinos). Any comment which has those words (either in the URL, comment body or email) is held for moderation.
However, this method is not perfect. For example, the default word list does not contain the words "poker" or "anti-wrinkle cream". I use a combination of Bloglines (my feed reader) and my "Comments RSS" feed. I have subscribed to my "Comments RSS" using Bloglines. This enables me to keep an eye on what comments have been posted on the site.
An aside: Interestingly, I have seen that the spammers target the articles which are older rather than the ones that are fresh. (i.e. my posts of November receive more spam comments as compared to the December ones). I guess, the idea is that once the articles have been moved off from the front page, not many users bother going back to the archives.
Whenever a new comment appears on the blog, I can either respond to it (if it is legitimate comment) or in a quick glance check out what new words the spammers are linking to. Add the new words to the Wordpress's blacklist, rerun the comments through the new blacklist, remove the comments that have been trapped and you are back in business with a spam-comment free blog.