Traumatic experiences are a risk factor for suicide and non-suicide self-injury. However, it has been hypothesized that the relation between trauma and self-harm is not a direct one, rather it is mediated by dissociation. The scope of this work is to review advances in psychopathology and pathophysiology of dissociation and its role in the context of stress-related disorders. Furthermore, a systematic review on the mediating role of dissociation between trauma and self-harm has been carried out. The systematic review confirms robust evidence of a mediating role of dissociation between trauma and non-suicidal self-injury; suicidal ideation and complete suicide as outcomes have not been addressed in the literature and need further assessment.