While early efforts in psychiatry were focused on uncovering the neurobiological basis of psychiatric symptoms, they made little progress due to limited ability to observe the living brain. Today, we know a great deal about the workings of the brain; yet, none of this neurobiological awareness has translated into the of psychiatry. The categorical system which dominates psychiatric diagnosis and thinking fails to match up to the real world of genetics, sophisticated psychological testing, and neuroimaging. Nevertheless, the American Psychiatric Association (APA) recently published a position paper stating that neuroimaging provided no benefit to the diagnosis and treatment of psychiatric disorders. Using the diagnosis of depression as a model, we illustrate how setting aside the unrealistic expectation of a pathognomonic “fingerprint” for categorical diagnoses, we can avoid missing the biological and, therefore, treatable contributors to psychopathology which can and are visualized using functional neuroimaging. Infection, toxicity, inflammation, gut-brain dysregulation, and traumatic brain injury can all induce psychiatric manifestations which masquerade as depression and other psychiatric disorders. We review these and provide illustrative clinical examples. We further describe situations for which single photon emission computed tomography (SPECT) and positron emission tomography (PET) functional neuroimaging already meet or exceed the criteria set forth by the APA to define a neuroimaging biomarker, including the differential diagnosis of Alzheimer’s disease and other dementias, the differential diagnosis of ADHD, and the evaluation of traumatic brain injury. The limitations, both real and perceived, of SPECT and PET functional neuroimaging in the field of psychiatry are also elaborated. An important overarching concept for diagnostic imaging in all its forms, including functional neuroimaging, is that imaging allows a clinician to eliminate possibilities, narrow the differential diagnosis, and tailor the treatment plan. This progression is central to any medical diagnostic process.Copyright © 2020 Henderson, van Lierop, McLean, Uszler, Thornton, Siow, Pavel, Cardaci and Cohen.