Depersonalization/derealization disorder is characterized by depersonalization often co-occurring with derealization in the absence of significant psychosis, memory, or identity disturbance. Depersonalization/derealization is categorized as one of the dissociative disorders, which also includes dissociative amnesia, dissociative fugue, dissociative identity disorder, and forms of dissociative disorder not otherwise specified. Although these disorders may be under-diagnosed or misdiagnosed, many persons with psychiatric illness who have experienced trauma report symptoms consistent with dissociative disorders. There are limited scientific data on prevalence of depersonalization/ derealization disorder specifically. This paper reviews clinical, phenomenological and epidemiological information regarding diagnosis and treatment of dissociative disorders in general, and illustrates common presenting histories of persons with derealization/depersonalization disorder utilizing composite cases. The clinical vignettes focus on recommended psychotherapy and pharmacotherapy interventions as part of a comprehensive multidisciplinary treatment plan for these individuals.