Research suggests that many mental disorders-mood and anxiety, substance use, and personality psychopathology-are related through relatively few latent transdiagnostic factors. With regard to the comorbidity of personality disorders and common mental disorders, factor structures such as internalizing-externalizing have been replicated in numerous samples, across the life span, and around the globe. One critical feature of transdiagnostic factors is that they serve as a point of intersection between personality and psychopathology, making them particularly relevant phenomena for applied clinical work. Although numerous studies have supported the significance of transdiagnostic factors for research and classification purposes, there has been comparatively less articulation of how such factors might be of benefit to practicing assessment clinicians. Herein, we present an overview of transdiagnostic factor research findings, and we apply these findings to the clinical topics of assessment, diagnosis, and treatment. For clinicians as well as researchers, the use of transdiagnostic constructs presents positive implications for efforts to understand, characterize, and ameliorate psychopathology-including its manifestations as personality disorder-in a valid, effective, and efficient way.