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Although early editions of the Diagnostic and Statistical Manual of Mental Disorders (DSM; Alliance of Psychoanalytic Organizations, 2006) incorporated a broad array of psychodynamic concepts, the influence of psychoanalysis in the DSM series has waned with each successive revision. The depsychoanalyzing of the DSM had a number of negative effects (e.g., increased syndrome comorbidity, diminished clinical utility). This article discusses how psychoanalytic concepts—once central but now marginalized—have much to contribute to DSM-6. I examine several ways in which a psychodynamic perspective can enhance the diagnostic manual, and challenges that may arise when psychodynamic concepts are reintroduced. I then present a psychodynamically informed framework for diagnosis in DSM-6 and beyond, which incorporates information in 4 domains: (a) overall level of functioning, (b) symptoms and syndromes, (c) underlying dynamics (i.e., ego strength, defense style, object relations), and (d) contextualizing factors (i.e., culture, stress, resilience and adaptation). I note how key constructs can be operationalized by clinicians and clinical researchers, and how dynamic assessment data can be integrated with descriptive, symptom focused information to enhance diagnosis and facilitate treatment planning.