Self-other distinction refers to the ability to distinguish between our own and other people's physical and mental states (actions, perceptions, emotions etc.). Both the right temporo-parietal junction and brain areas associated with the human mirror neuron system are likely to critically influence self-other distinction, given their respective contributions to theory of mind and embodied empathy. The degree of appropriate self-other distinction will vary according to the exact social situation, and how helpful it is to feel into, or remain detached from, another person's mental state. Indeed, the emotional resonance that we can share with others affords the gift of empathy, but over-sharing may pose a downside, leading to a range of difficulties from personal distress to paranoia, and perhaps even motor tics and compulsions. The aim of this perspective paper is to consider how evidence from behavioral and neurophysiological studies supports a role for problems with self-other distinction in a range of psychiatric symptoms spanning the emotional, cognitive and motor domains. The various signs and symptoms associated with problematic self-other distinction comprise both maladaptive and adaptive (compensatory) responses to dysfunction within a common underlying neuropsychological mechanism, compelling the adoption of more holistic transdiagnostic therapeutic approaches within Psychiatry.