Studies of the postmortem human brain have become an increasingly essential element of the effort to understand the neurobiology of psychiatric disorders, especially in light of advances in our knowledge of functional brain circuitry and the new opportunities to apply the approaches of genomics and proteomics. This Perspective reviews some of the opportunities afforded by investigations of the postmortem human brain, and offers suggestions for improving the quality of future studies through the use of well-characterized brain specimens, well-constructed experimental designs and well-controlled confounds.