We have developed a high throughput microarray-based approach for gene function screens in stem cells. Our microarrays are generated using soft lithographic microfabrication techniques; the method can be used for both loss and gain of function screens, and is compatible with both adult and embryonic stem cells. The method allows us to assay in parallel various cell functions including signaling, differentiation, and proliferation. To demonstrate the utility of this approach, we have screened cDNA libraries for factors that affect adult neural stem cell function. Our method would facilitate genome-scale gene function studies in a variety of mammalian cells, as well as the identification of drug targets and the generation of therapies for neurodegenerative diseases.