This paper is written from a psychodynamic clinician's perspective, juxtaposing a psychoanalytic-attachment model of depression with recent developments in neuroscience. Three main components of the attachment approach are described: the role of loss, of childhood trauma predisposing to depression in later life, and failure of co-regulation of role of primitive emotions, such as fear, despair, and helplessness. Blatt's distinction between anaclitic and introjective depression is delineated and related to hyper- and de-activation of the attachment dynamic. Recent advances in evolutionary, sociological, epigenetic, biochemical, and neuro-imaging studies of depression are reviewed. A dynamic model of depression is proposed, linking interpersonal and intra-psychic perspectives with neuro-anatomical models. The final section of the paper considers the specific role of psychodynamic approaches to the treatment of refractory depression. These include length of treatment, capacity to rework implicit memories, and focus on transference and counter-transference.