Explanatory models in psychiatry reflect what clinicians deem valuable in rendering people's behavior intelligible and thus help guide treatment choices for mental illnesses. This article outlines some key scientific and ethical principles of clinical explanation in twenty-first century psychiatry. Recent work in philosophy of science, clinical psychiatry, and psychiatric ethics are critically reviewed in order to elucidate conceptual underpinnings of contemporary explanatory models. Many explanatory models in psychiatry are reductionistic or eclectic. The former restrict options for diagnostic and therapeutic paradigm (...) choice, while the latter lack a well-defined theoretical basis. These two methodological approaches stand in a dialectical relation to one another insofar as clinicians often move from one approach to its antithesis, ultimately seeking a synthesis of the two approaches that satisfies clinical needs. Pragmatic considerations can help to transcend the reductionism/eclecticism dialectic. In the absence of a completed science of mental disorders, psychiatrists must tolerate ambiguity and uncertainty as they strive to integrate diverse explanatory concepts in a rigorous and evidence-based fashion. A pragmatic explanatory model in clinical psychiatry must focus on favorable treatment outcomes for patients by respecting the pluralistic, participatory, and provisional nature of psychiatric explanation. (shrink)