Imaginary insect or mite infestations, a condition called delusional infestation (DI), are not uncommon in the human population. Pest control technicians, entomologists, and physicians (especially dermatologists) frequently encounter these patients who complain of mystery bites or itches which they attribute to tiny insects or mites. Patients characteristically produce numerous samples containing tiny bits of debris, lint, hair, fibers, and sometimes scabs and skin. This chapter provides in-depth coverage of the condition of DI, its various contributing factors, and treatment strategies. A related condition, Morgellons disease, is also presented and discussed.