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Basic psychodynamic assumptions such as the influence of early development on ways to cope with disease and associated existential issues, defense mechanisms operating in situations of threat, or the role of transference in the clinician-patient encounter will be illustrated and discussed by means of patient vignettes. More generally, the clinics of palliative care can be conceived as a clinic of loss; a psychodynamic perspective on loss, grief and depression can also be a key to comprehend and critically review the recent developments of psychological interventions aiming to counteract the experience of loss in the palliative care setting.