Histone modification and noncoding RNAs are emerging players in gene regulation and human disease. Here I will present our studies on how histone modifications and noncoding RNAs control human gene expression pertaining to steroid signaling, lipid metabolism, inflammation, cardiovascular diseases, and cancer. We will also present on how chromatin modifying enzymes and noncoding RNAs can be used as potential biomarkers and therapeutic targets for various human diseases.