Depersonalisation (DP) and derealisation (DR) are subjective experiences of unreality in, respectively, one's sense of self and the outside world. These experiences occur on a continuum from transient episodes that are frequently reported in healthy individuals to a chronic psychiatric disorder that causes considerable distress (depersonalisation disorder: DPD). Despite the relatively high rates of reporting these symptoms, little research has been conducted into psychological treatments for this disorder. We report on an open study where 21 patients with DPD were treated individually with cognitive behavioural therapy (CBT). The therapy involved helping the patients re-interpret their symptoms in a non-threatening way as well as reducing avoidances, safety behaviours and symptom monitoring. Significant improvements in patient-defined measures of DP/DR severity as well as standardised measures of dissociation, depression, anxiety and general functioning were found at post-treatment and six-months follow-up. Moreover, there were significant reductions in clinician ratings on the Present State Examination (Wing, Cooper & Sartorius, 1974), and 29% of participants no longer met criteria for DPD at the end of therapy. These initial results suggest that a CBT approach to DPD may be effective, but further trials with larger sample sizes and more rigorous research methodology are needed to determine the specificity of this approach.