Dissociation is a dysfunction of normally integrated functions like memory, consciousness and perception of environment. This review discusses the clinical and etiological issues of dissociative disorder and highlights the importance of differential diagnosis and psychiatric comorbidities, with special attention for the development of reliable evaluation instruments and treatment guidelines. New approaches of dissociative disorder focus on the importance of the integration of anatomical and functional neuroimaging data, combined with endocrinological and biological studies (lipids), in order to develop some specific neurobiological models. Beyond the inherent singularity of psychotherapeutic intervention, the therapeutic approach varies according to frequently associated comorbidities.