The study of postmortem human brain tissue is central to the advancement of neurobiologic studies of psychiatric and neurologic illnesses, particularly the study of brain-specific isoforms and molecules. Due to tissue demands, especially pertaining to brain regions strongly implicated in the pathophysiology of neuropsychiatric disorders, the success and future of this research depend on the availability of high-quality brain specimens from large numbers of subjects, including nonpsychiatric controls, both of which may be obtained from brain banks. In this chapter, we elaborate on the need for and acquisition of well-curated and properly diagnosed postmortem human brains, relying upon our experience with the Human Brain and Tissue Repository located at the Lieber Institute for Brain Development in Baltimore, MD. We explain the advantages of sourcing postmortem human tissue from medical examiner offices, which provide access to cases of all ages, both with and without central nervous system disorders. Neuropathology analyses and toxicologic screenings, along with autopsy reports and extensive interviews with family members and treating physicians, are invaluable to the diagnoses of postmortem cases. Ultimately, the study of psychiatric and neurologic disorders is the study of brain disease, and accordingly, there is no substitution for human brain tissue.