Genetics cannot solely explain genetic variations in humans and disease developments. We see varying differences in phenotypes and disease susceptibility in organisms that have the same genetic make-up, e.g., monozygotic twins and cloned animals. The information carried by the genomic sequence is the blueprint, but the final product requires environmental determinants. Here comes the concept of epigenetics, as it is the framework where biochemical interactions between the genome and the environment blend. We can describe epigenetics as mechanisms that are beyond genetics, as such mechanisms alter the result of the genomic blueprint without altering the information itself, i.e., the sequence. Both epigenetics and epigenomics are trending research fields to better evaluate the genotype and the phenotype. The methylation of genetic material is a well-studied and well-known epigenetic marker. The epigenome, as a term, describes the inheritable changes in both the DNA and histone molecular structures, where the methylation and acetylation mechanisms are studied extensively. As the building blocks of the chromatin structure, nucleosomes depend on epigenetic changes, which lead to becoming either tight or loose, based on the particular mechanisms. Chromatin structure changes directly affect the gene expression, e.g., particular gene expression becomes silenced if the gene position has DNA hypermethylation and histone hypoacetylation that leads to the condensed form of the chromatin. Inversely, if the said changes were removed, genes in that position would express themselves again. Therefore, epigenetics provides a vigorous and remarkably malleable means for gene expression regulations. Epigenomics includes both the epigenetic mechanisms on the DNA and histones and complicated interactions between the genotype and the phenotype. There are well-known epigenomic changes in DNA, RNA, and protein levels. DNA base changes in somatic cells and chromosome positioning are among the aspects determining the epigenomic scene. Alternative splicing mechanism, RNA processing (editing, capping, Poly-A tailing, etc.), RNA methylation, and regulations conferred by the non-coding RNAs (ncRNAs) are RNA level epigenomic changes. Epigenomic changes at the protein level include various mechanisms of the post- translational modification. Epigenomics research includes total hypomethylation profile of the genome, identification of hypermethylated genes, microRNA-driven gene silencing with DNA methylation, epigenome projects, and DNA-based clinical therapies for different biomedical conditions. This chapter will detail fundamental concepts and basic approaches to both epigenomics and epigenomes.