DNA microarrays are powerful tools for the analysis of the organization and regulation of the brain, in both illness and health. Such messenger RNA expression methods are outgrowths of a marriage between the several genome sequencing projects and a wide variety of physical, chemical, optical, and electronic systems. The advantages of microarray analyses include the ability to study the regulation of several genes or even the entire genome in a single experiment. However, there are substantive issues associated with the use of these tools that need to be considered before drawing conclusions about the genomic regulation of the brain. These issues include the loss of most anatomic (i.e., cellular and circuit) specificity, only fair sensitivity, lack of absolute quantitative data, poor comparability between studies, and high variability in sample values, to mention the most obvious. In this review we point to some of the solutions proposed for these problems and novel techniques and approaches for newer methods. Among these are methods for making arrays more sensitive, including nonarray messenger RNA expression systems. The future of this field and its links to deeper protein and cell biology are both emphasized.