Morgellons disease is a mysterious skin disorder that was first described more than 300 years ago. The disease is characterized by fiber-like strands extruding from the skin in conjunction with various dermatologic and neuropsychiatric symptoms. In this respect, Morgellons disease resembles and may be confused with delusional parasitosis. The association with Lyme disease and the apparent response to antibacterial therapy suggest that Morgellons disease may be linked to an undefined infectious process. Further clinical and molecular research is needed to unlock the mystery of Morgellons disease.