A contemporary model for the pathogenesis of mood disorders (bipolar and depressive disorders) involves gene-environmental interaction, with genetic predisposition, epigenetic regulation, and environmental effects. Among multiple environmental factors, the experience of childhood trauma can be connected with the pathogenesis, course and the treatment of mood disorders. Patients with mood disorders have the greater frequency of childhood trauma compared with the general population, and adverse childhood experiences can exert a negative impact on their clinical course. In this article, the neurobiological mechanisms of childhood trauma are presented. The influence of negative childhood experiences on the central nervous system can result in many structural and functional changes of the brain, including such structures as hippocampus and amygdala, associated with the development of bipolar and depressive illnesses. Interaction of several genes with childhood trauma to produce pathological, clinical phenomena in adulthood has been demonstrated, the most important in this respect being the serotonin transporter gene and the FKBP5 gene playing an important role in the pathogenesis of mood disorders. Neurobiological effects can also involve epigenetic mechanisms such as DNA methylation which can exert an effect on brain function over long-term periods. Somatic effects of childhood trauma include disturbances of stress axis and immune-inflammatory mechanisms as well as metabolic dysregulation. Negative childhood experiences may also bear implications for the treatment of mood disorders. In the article, the impact of such experiences on the treatment of mood disorders will be discussed, especially in the context of treatment -resistance to antidepressants and mood-stabilizing drugs.