We propose a transdiagnostic approach that centers on modes, state-like manifestations of personality that function as cohesive organizational units. Modes are characterized by specific profiles of affects, behaviors, cognitions, and desires that tend to be coactivated. Each mode is typically experienced as having its own distinct experiential and agentic qualities. A mode-based approach to psychopathology builds on recent analytic and methodological developments which demonstrate the value of modeling personality states dynamically, as well as on longstanding theoretical and empirical traditions that highlight the pragmatic clinical utility of such conceptualizations. We seek to illustrate how the conceptualization of psychopathology in terms of modes and their dynamic interrelations holds considerable transdiagnostic promise. As background, we review both theory and research from philosophical accounts of selfhood, developmental psychology, social and personality psychology, and diverse psychotherapy models that lay the foundation for this mode-based approach to psychopathology. We elaborate on this foundation and (in Section 1 of our online supplemental materials) provide examples of the approach's explicit or implicit relevance to several classes of psychopathology, including dissociative, trauma-related, mood, anxiety, obsessional, substance, psychotic, and personality disorders. After addressing the clinical utility of mode-based conceptualizations, we lay out a research blueprint for assessing and modeling modes, and (in Section 2 of the online supplemental materials) present a broader research agenda highlighting intriguing empirical questions regarding modes in psychopathology. We conclude by noting that the time seems ripe for modes to be (re-)introduced as an organizing construct for understanding psychopathology and personality. (PsycInfo Database Record (c) 2023 APA, all rights reserved).