The only massive threats that could harm us that would be hard to see would be large objects of shadow matter that may have some effect--but I think its gravity would be detected. Perhaps our space probes are being influenced by some kind of strange object. Doubtful, but...

http://physicsweb.org/articles/news/9/12/4/1

"They believe there may be, on average, one dark-matter ball for a volume of space about the size of our solar system (Phys. Rev. Lett. 95 231301)."