Nuclear receptor (NR) target genes have key roles in cellular metabolism, cellular growth and differentiation and in controlling inflammation. Many NR target genes are also involved in dysregulated pathways that can lead to common human diseases, such as type 2 diabetes, atherosclerosis, Alzheimer’s disease and cancer. On the genomic level these pathways converge on regulatory modules, some of which contain co-localizing NR binding sites, so-called response elements (REs). Recent advances in genomic techniques combined with computational analysis of binding modules are discussed in this chapter, primarily at the example of the NRs vitamin D receptor (VDR or NR1I1) and peroxisome proliferator-activated receptors (PPARα or NR1C1, PPARβ/δ or NR1C2 and PPARγ or NR1C3).