Investigating relations between psychological factors and DNA-damage can contribute to understanding how psychological factors affect the etiology and prognosis of relevant diseases (e.g., cancer, heart disease) at the fundamental level of mutated cells. This article critically reviews 21 studies in animals and humans testing relations between psychological factors and DNA-damage. After providing a biological background, we critically review each study. The findings in humans are mapped onto a model of stress, coping and health. These studies demonstrate causal relations between acute stressors and DNA-damage in animals and significant correlations between psychological factors (e.g., depression, coping) and DNA-damage in humans, which are moderated by gender. Possible mechanisms for these relations, limitations of studies, clinical implications and suggestions for future research are provided.