Gene sets are groups of genes linked by function, regulation or other features that make them useful in identifying trends within large molecular datasets. The ENCODE project has conducted a wealth of genomics profiling experiments that has proven to be a valuable reference data resource for the study of how genes are regulated. ENCODE Gene Set Hub (EGSH), a growing resource of gene sets derived from high quality ENCODE profiling experiments encompassing hundreds of DNase hypersensitivity, histone modification and transcription factor target experiments. As demonstrated by some of our groups’s previous articles, this approach in tandem with pathway level tools such as Gene Set Enrichment Analysis (GSEA), is useful in identifying chromatin-level regulators involved in the response to various stimuli. So far, we have included human and mouse gene sets, but this will expand to include ModENCODE organisms; fly and worm. We will also be including other experiment types to generate gene sets based on RNA-seq, DNA methylation and chromatin conformation. Closer to the conference date these gene sets and the underlying code will be made public. These gene sets will become an essential resource for investigators undertaking pathway level studies.