Clarity about the intended targets of treatment is, by necessity, a prerequisite for any psychiatric or other medical intervention. One cannot make sensible treatment decisions unless one knows with some degree of confidence what exactly constitutes the object of treatment. Yet, by and large, psychiatric diagnoses are made on purely clinical grounds – meaning, they derive from collections of signs and symptoms that cohere in an organized fashion, seldom with definitive corroboration by an external biomarker. (Some exceptions to this might include positive blood or urine toxicology screens to affirm the diagnosis of alcohol or other substance intoxications; low cerebrospinal fluid levels of orexin to diagnose narcolepsy; or neuroimaging or other laboratory tests that affirm an underlying nonpsychiatric medical condition (such as a brain malignancy, or metabolic derangement) that might explain an acute mental status change.) Herein lies a dilemma: while evidence-based treatment means identifying a plausible working diagnosis, categorical diagnoses cannot always be made with the degree of exactitude one might otherwise hope for.