A condition in which a male best friend of a girl is in love with said girl, but is constantly shot down or ignored in favor of other men. When he does finally get a chance to admit his feelings, he is most often rejected in favor of being 'just friends' and will never get a chance to be with the girl again. There is no cure for Jacob Syndrome except to somehow find a girl you are even more in love with.
Joe: Olivia, I love you, and I always have.
Olivia: But Joe, I just want to be friends. Can't you understand?
Joe: Fucking Jacob Syndrome.