Among its several changes and innovations, the second edition of the Psychodynamic Diagnostic Manual (PDM-2) strongly emphasizes the importance of the therapeutic relationship. The manual helps clinicians to understand better their behaviors in therapy with different patient groups, to guide therapeutic interventions, to track in-session processes, to deal with ruptures in the therapeutic alliance, and to achieve a better therapy outcome. In this article, we examine the clinical implications of the PDM-2 Adult M Axis (i.e., the Profile of Mental Functioning). We begin by describing the structure and main features of the M Axis. We then outline how a psychodynamically informed assessment of the mental capacities involved in a patient’s overall psychological health or pathology can provide therapists with useful insight into the development of the therapeutic alliance. We discuss 2 items of a clinical measure developed by our research group (the Collaborative Interactions Scale—Revised), to illustrate their interplay with specific M-Axis mental capacities and the role of this interplay in determining both patients’ and therapists’ contributions to the therapeutic alliance. Finally, we provide a clinical illustration and commented excerpt, along with the patient and therapist assessments of M-Axis capacities.