In this article we present personalized psychotherapy, a treatment approach for people with a wide range of personality problems and clinical syndromes that is a central part of Theodore Millon's unified clinical science model of personality and psychopathology. Because the intervention strategy is fully integrated with an evolutionary perspective on human development, we offer it in this context. We begin with a historical overview of Millon's model and its relationship to the Diagnostic and Statistical Manual of Mental Disorders (DSM). We then present his basic theoretical principles and personality taxonomy, and discuss variations in personality functioning across the normal–abnormal continuum. We move on to describe assessment measures that were developed to operationalize his concepts and ideas, and which are used as the basis for creating treatment plans. The premises and principles of personalized psychotherapy are described to show how the intervention model is squarely focused on the integrated unity of the person. We look at presenting problems of all kinds from the point of view of how they emanate from, and are related to, the individual's unique combination of temperament, traits, preferences, behavioral patterns, and coping strategies. We then specify multimodal interventions (e.g., a combination of pharmacologic, cognitive, behavioral, phenomenological, interpersonal, and/or intrapsychic treatments) and apply them in a particular sequence to maximize their impact, not only on the target symptoms, but on the underlying personality elements believed to be their primary cause.