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In recent decades, the evidence base for psychodynamic psychotherapy has expanded considerably, allowing for the application of treatments like transference-focused and mentalization-based therapies to a host of psychiatric concerns across a variety of contexts (Bateman & Fonagy, 2004, 2008, 2015, 2016; Constantinides & Dauphin, 2023; Griffiths et al., 2019; Yeomans et al., 2015). As that evidence base expands, we find that these therapies are particularly applicable to individuals with comorbid personality disorders and treatment-resistant depression. We aim in this special section to review the ways this is supported by research, with particular focus on mentalization-based treatment. This section will begin by stating the relevance of mentalizing to good mental health and, further, how comorbid personality pathology and treatment-resistant depression present distinct challenges to mentalizing. Then we elaborate on imbalances in mentalizing, how these difficulties underpin personality pathology, amplify depression, and manifest differently across personality types. This leads to a review of mentalization-based approaches, namely the more structured treatment model and the informal application of a mentalizing framework. To illustrate the effect of a treatment using the mentalizing framework, a case example is offered using a novel method of mentalizing assessment (incomplete sentence task). The use of three regularly administered sentence completion tasks at the beginning, middle, and end of treatment observed linguistic and qualitative changes in the patient's mentalizing. We close with conclusions about this novel method and the potential for mentalization-based approaches for those with comorbid personality pathology and treatment-resistant depression, with ideas for future directions.