The most frequently used method of hiding malware on a machine is the use of a rootkit. (See Sony's blunders) This is a method that's been discovered quite recently - first appearing (to my knowledge) in about 1978.
It can be quite effective, and can be difficult even to detect, much less remove. Some security analysts in fact have advocated the policy that any evidence of any kind of infection is reason to reformat all the hard drives and reinstall everything. I don't know that anyone's actually applying that policy - yet.
There is no clear leader for "best detection and removal" program, but there are a couple of "leaders" in reporting of new exploits. One that pops up frequently in the news is F-Secure, and some other active reporters fairly frequently report finding things using F-Secure programs.
I haven't tried their stuff, so can't really say what it does or how good it is, but one of their products is at F-Secure Blacklight. I believe it was a free download during beta, but may have been incorporated into a security suite that requires purchase.
There are a few others, and some have received "good mentions;" but nobody has been publishing comparative reviews, so information has to be searched out.