A number of microarray investigations using human postmortem brain tissue have been published recently, exploring a multitude of human brain disorders with the aim of unraveling the underlying pathologies. Although the technology is still developing and lacks sufficient sensitivity with regard to detecting splice variants and low abundance transcripts, microarrays are becoming the prominent method for candidate gene screening in complex neuropsychiatric disorders. The use of postmortem tissue harbors a variety of potential pitfalls, however, which could result in unreliable or, at worst, meaningless results. During the course of our large-scale gene expression study on 150 human postmortem brain samples, using more than 200 Affymetrix GeneChips, we have identified several aspects within microarray experimental procedure that allows for the early identification of potentially unreliable samples. The general application of the guidelines and technical tips described here increase the efficiency, reliability, and amount of data generated by this powerful screening technology while reducing superfluous consumption of time and resources.