Treatment-refractory mood disorders pose a significant problem for clinicians. Although biological approaches are usually emphasized in the treatment of patients with these disorders, preliminary findings from an ongoing, naturalistic, longitudinal study of treatment outcome support the notion that a subset of patients with treatment-refractory mood disorders may respond to careful integration of a psychodynamic therapeutic approach into the customary biological approaches. Ten psychodynamic principles that appear to be useful in work with patients with treatment-refractory mood disorders were identified based on a review of the records of 28 patients who were treated using this approach. These principles are presented, discussed, and illustrated by material from a representative case study.