W is for Werewolves
Although I'm generally more of a vampire person, the Daniel Osbournes of the world make sure I always hold a place for werewolves as well. In fact, I told Dr. Nerd when I was pregnant with our youngest that I was going to call him Oz as a nickname, regardless of what we ended up naming him.
He even made sure to time his birth with the ancient Roman festival of Lupercalia. So of course he's our young Wolf.
W is for Werewolves
Contrary to how it works in fiction, in real life werewolves are way older than vampires. Vampirism as a trait has been around just shy of forever, but modern bloodsuckers are only a couple hundred years old while lycanthropes have been around for millennia. They have been hunted not only for their pelts, but also to burn alongside witches.
Hypertrichosis (which basically means a lot of hair) is an obvious possibility as far as a medical explanation for werewolves, but as it's vanishingly rare, I think it's silly to even bring it up. Despite the fact I just did.
Much like vampires, I like rabies as a potential explanation. There's the connection with an animal foaming at the mouth and raving. People suffering from rabies experience confusion that makes others view them as animalistic. Not-so-fun-fact: Once symptoms appear, rabies is 100% fatal. DO NOT WAIT if you receive a suspicious bite. You will not become a werewolf.
Really though it just seems silly to even make guesses as to any original explanation of werewolves from two thousand years back or more. Maybe it was made up as a fairy tale to keep the kids from wandering off too far on their own, but the game of telephone got everything mixed up and the fiction of it was lost along the way. (That's why we write this stuff down, Socrates!)
Werewolves? Why not?
A while back, I was in a conversation about whether vampires or werewolves were more possible, using actual current scientific knowledge. The content of that conversation led to me writing a novel based on our conclusion - that werewolves didn't seem very probable.
The biggest problem we came up with on the werewolf side was conservation of mass. If the wolf and person are comparable size that's not a problem, but when you have a teeny person transforming into a giant wolf twice their size it is. How are they going to knock anything down if they're only half density?
At Mad Art Lab, though there's a thoughtful piece that addresses the problems we came up with and more, and offers some science(ish) solutions.