Personality describes an enduring pattern of experiences and behaviors in the interpersonal and social sphere. Several aspects of personality, e.g., defenses, relational dynamics, and reactions, are commonly accentuated in the midst of medical care; therefore, understanding a patient's personality allows the clinician to make informed predictions about how a specific patient may respond to illness and how care interactions might be modified to optimize care engagement and outcomes.This article provides a brief description of the personalities in the Psychodynamic Diagnostic Manual, Second Edition, and discusses how each one might inform clinical interactions. Two additional personality-like presentations-the traumatized patient and cognitive impairment-are included for clinical utility given their high prevalence in medical settings and their potential for broad impact on clinical relationships.Personality-informed care is an approach that incorporates information about the patient's personality into the clinical relationship. It describes what the clinician might say and when, what recommendations to offer and how to frame them, and how to comport oneself while providing care.Personality-informed care operationalizes several aspects of personalized medicine, and it offers a heuristic framework that may facilitate and enhance the implementation of evidence-based care.