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This article reviews moderators and mediators of therapeutic change through the lens of the two-polarities model of personality development. This psychodynamic model of personality development essentially proposes that personality development involves a continuous dialectic interaction between the development of the capacity for relatedness on the one hand and agency and self-definition on the other. Within this model, vulnerability for psychopathology is thought to result from an excessive emphasis on one developmental line and the defensive avoidance of the other. The two-polarities model also proposes a unified, transdiagnostic approach to therapeutic change in that it suggests that effective interventions, regardless of the brand name, lead to a reactivation of the dialectic interaction between the development of relatedness and self-definition through experiences of mutuality and understanding, as well as separation and misunderstanding in the therapeutic relationship, much as in normal personality development. We summarize research relevant to this view, and illustrate how this empirically based model of personality development and the therapeutic process may inform clinical practice. We focus specifically on recent developments within this model, which have led to a major shift in our thinking regarding the role of specific and common factors in explaining therapeutic change. We illustrate this shift in our thinking by way of a discussion of emerging research findings concerning therapeutic change in both brief and longer-term treatments across different therapeutic modalities. Limitations of the model are reviewed, and suggestions for future research are discussed.