Yesterday, there was an article online at Scientific American discussing scientists' efforts to map dark matter in space. If you're not familiar with dark matter, don't worry; no one really is. It's material that can interact with ordinary matter through gravity but is otherwise undetectable. Dark matter may make up as much as 98% of the universe, but it doesn't seem to be present on Earth, only in space.
Although I'm no expert on this branch of science, I find it fascinating that there's so much out there we don't know about yet. If scientists ever discover the nature of dark matter, we could be in for another paradigm shift, like the ones Kuhn talks about in The Structure of Scientific Revolutions. (I still remember that from my History of Science class during undergrad.) I attended a panel on dark matter in science fiction last year at WisCon; you can read my notes here if you're interested.
What areas of science do you think we know the least about?