A recently established transfected cell array (TCA) technology has opened new experimental dimensions in the field of functional genomics. Cell arrays allow for transfection of several thousands different DNA molecules in microarray format. The effects of overexpression of hundreds of proteins on cellular physiology can be observed in a single experiment. The TCA technique has also found its application in RNA interference (RNAi) research. Small interfering RNAs (siRNA) as well as plasmid expressing short hairpin RNAs can be transferred into the cells through the process of reverse transfection. The silencing of numerous genes in spatially separated manner can be thus monitored. This review will provide an overview on current concepts concerning combination of cell array and RNAi for high-throughput loss-of-function studies.