Normally, Akismet does a very good job of weeding out spam. I’ve actually never had a spam comment make it through, and to my knowledge, haven’t had a “false positive,” either.
I can’t say I get a huge amount of traffic, but in the couple years I’ve had my blog at wordpress.com, Akismet has blocked over 15K spam messages. I do look at them at least every other day to make sure that there’s no legitimate email that’s been accidentally blocked as spam, but that takes less than a minute, then I empty the spam.
What sort of spam are you seeing that makes it past the filter?