The therapeutic alliance is one of the most consistent predictors of therapeutic change, including symptom reduction and improvement in wellbeing and quality of life, across a variety of mental health interventions. Yet, little is known about its biological mechanisms. Oxytocin (OT) has been suggested as a biological mechanism by which bonds are formed and strengthened across species. This article is intended to demonstrate the potential of OT as a biomarker of therapeutic change in psychotherapy and counseling psychology, especially of the therapeutic alliance. We delineate three main potential paths of investigation based on the most recent research on OT in parent-child and romantic partner dyads. For each path, we provide a detailed explanation for whom, when, and how OT should be measured. Each path is illustrated using data collected in a randomized controlled trial of psychotherapy for major depressive disorder. These illustrations demonstrate the great potential of OT as a biomarker of (a) trait-like characteristics of the patients and the therapists, (b) the processes of therapeutic change, and (c) the dyadic synchrony between patients and their therapists. The potential clinical contribution of OT as a biomarker for each of these three paths is further demonstrated using a case study. Practical suggestions and directions for future research are discussed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).