Gene expression analysis of microarray data can provide a global view of the transcriptome of a cell or specific tissue type, revealing important information about the kinds of signaling pathways, genes and protein classifications that are active. However, transcript profiles alone do not reveal how expression levels are controlled or which transcription factors (TFs) are responsible. Establishing transcriptional regulatory networks requires knowledge of TFs bound to promoter, enhancer and repressor elements. Accessibility of these sites and an additional level of control are mediated by chromatin and DNA modifications. Genome-wide location analysis is a tool for identifying protein-DNA interaction sites on a genomic scale. Applications of this tool are proving invaluable in determining in vivo target genes of TFs, epigenetic marks and cis-regulatory elements. Here, we will discuss how advances have been made in each of these categories and how this has helped to elucidate regulatory networks and control mechanisms.