Moral behaviour requires at least two components: 1) knowing about socio-cultural norms and the needs of others (i.e. social knowledge), and 2) being motivated to act on this knowledge (i.e. moral motivation and emotion). There is emerging evidence from neuroimaging in healthy participants as well as patients with frontotemporal dementia that abstract social knowledge (i.e. knowledge of social concepts such as “greed”) is stored in the superior anterior temporal cortex, especially within the right hemisphere. Different moral emotions (guilt or indignation) are associated with the same social concepts (e.g. “greed”) depending on the context (oneself or someone else behaving e.g. “greedily”). Interestingly, guilt and indignation shared activation within the anterior temporal cortex, whilst eliciting distinct activation patterns within frontal-subcortical networks. It is these distinctive neural signatures which are of interest to neuropsychiatry, because they could account for the clinical observation of selective disruption of particular types of moral emotions. The healthy experience of guilt was associated with septal, subgenual cingulate, and frontopolar activation. This was corroborated by showing that loss of guilt in patients with frontotemporal dementia correlated with neurodegeneration in septal and frontopolar areas. These neural signatures of guilt were distinctive when compared with indignation or anger towards others. Despite the theoretical importance of guilt and self-blame, first highlighted by Freud, their neural bases in major depressive disorder (MDD) were unknown. We recently addressed this question using fMRI. As predicted from our earlier work, overgeneralised self-blame (e.g. “feeling guilty for everything”) and MDD were associated with functional disconnection between the anterior temporal cortex and a septal-subgenual-frontopolar network when patients with MDD experienced guilt. Ongoing clinical translation of these findings including development of an fMRI biomarker of MDD recurrence risk and real-time fMRI-based neurofeedback interventions to enhance adaptive moral emotions, as well as interventions tackling overgeneralised self-blame will be discussed.