When an individual diagnosed with major depressive disorder does not respond sufficiently even after multiple adequate trials of otherwise effective treatments, the label treatment-resistant depression (TRD) is often used to describe the patient's condition. Personality disorders are among the most prevalent comorbid psychiatric conditions in major depressive disorder and, when undiagnosed or untreated, can contribute to the development of treatment resistance. This article provides an update on conceptualization and assessment of comorbid TRD and personality disorders and introduces three available evidence-based psychodynamic approaches to treatment: good psychiatric management, transference-focused psychotherapy, and mentalization-based treatment. This lead article for the special section on TRD and personality disorders is followed by companion articles on transference-focused psychotherapy, mentalization-based treatment, and mentalization more broadly.