Depersonalisation disorder involves an unpleasant, chronic and disabling alteration in the experience of self and environment. In addition to these classic features of depersonalisation and derealisation, symptoms may also encompass alterations in bodily sensation and a loss of emotional reactivity. Primary depersonalisation disorder is probably more common than previously thought, and here we discuss the diagnosis, assessment and treatment of the condition, with particular reference to our experiences in a specialist depersonalisation clinic. We also consider psychological and biological aspects of the condition. Although there is as yet no recognised treatment for this disorder, various pharmacological interventions, particularly a combination of lamotrigine and a selective serotonin reuptake inhibitor, have shown promise. We discuss these drug treatments, together with psychological approaches, in particular a recent cognitive–behavioural conceptualisation and treatment approach.