Alterations in serotonergic and noradrenergic receptor binding in membrane homogenates from the brain of suicide victims suggest a biological substrate for the vulnerability to commit suicide. We and others have employed high-resolution quantitative autoradiography of full coronal sections of the prefrontal cortex to map the locus of maximal change in receptor binding. We found alterations in binding to the serotonin transporter, the 5-HT1A, and the 5-HT2A receptors primarily in the ventral and ventrolateral prefrontal cortex of suicide victims. Importantly, these changes are often modest in magnitude and anatomically restricted to one or two Brodmann areas. Furthermore, we have found that care in case selection is essential, because sex, age, drugs, and comorbid diagnoses contribute to receptor binding. The implications for in vivo imaging are considerable, directing the focus of such studies toward the ventrolateral prefrontal cortex. However, because ligands are limited, as is the resolution of current methods, including PET, automated analyses that produce statistical images, rather than manual selection of individual slices, will likely lack the ability to detect the discrete receptor changes found postmortem. Alternatively, the advantages of examining large numbers of subjects, imaging the entire brain, obtaining detailed clinical information in the living patient, and magnifying the changes with neuropharmacological challenges present a promising outlook for making major advances into the identification of brain abnormalities associated with suicide risk.