The vitamin D receptor (VDR) is a ligand-inducible transcription factor whose target genes play key roles in cellular metabolism, bone formation, cellular growth, differentiation and in controlling inflammation. Many of these VDR target genes are also involved in dysregulated pathways leading to common human diseases, such as cancer. The activation of VDR by natural and synthetic ligands may improve such pathological conditions. On a genomic level, these pathways converge on regulatory modules, some of which contain VDR-binding sites, so-called vitamin D response elements (VDREs). Transcriptome analysis, chromatin immunoprecipitation scans and in silico screening approaches have already identified many genomic targets of the VDR. Important cancer regulatory modules with VDREs should have a major impact on understanding the role and potential therapeutic value of VDR in cancer.