The current review aims to unravel what is known regarding the neural substrates of empathicdistress and compassion fatigue. Empathic distress is a self-oriented feeling of anxietyexperienced in response to the suffering of another. It has been related to, and theorized to bea precursor of, compassion fatigue. This is a form of caregiver burnout received by secondaryexposure to trauma. In the current thesis, Scopus, Web of Science and PsycINFO weresearched identifying 301 articles that were subsequently screened. In the end, five studieswere included that measured either empathic distress or compassion fatigue in relation tobrain structure or function. Findings are largely inconsistent but areas involved in theory ofmind and that are important for the self-other distinction are discussed. A need for moreresearch is identified, together with a desire for conceptual clarification between compassionfatigue and burnout.