Essential genes refer to genes that are required by an organism to survive under specific conditions. Studies of the minimal-gene-set for bacteria have elucidated fundamental cellular processes that sustain life. The past five years have seen a significant progress in identifying human essential genes, primarily due to the successful use of CRISPR/Cas9 in various types of human cells. DEG 15, a new release of the Database of Essential Genes (www.essentialgene.org), has provided major advancements, compared to DEG 10. Specifically, the number of eukaryotic essential genes has increased by more than fourfold, and that of prokaryotic ones has more than doubled. Of note, the human essential-gene number has increased by more than tenfold. Moreover, we have developed built-in analysis modules by which users can perform various analyses, such as essential-gene distributions between bacterial leading and lagging strands, sub-cellular localization distribution, enrichment analysis of gene ontology and KEGG pathways, and generation of Venn diagrams to compare and contrast gene sets between experiments. Additionally, the database offers customizable BLAST tools for performing species- and experiment-specific BLAST searches. Therefore, DEG comprehensively harbors updated human-curated essential-gene records among prokaryotes and eukaryotes with built-in tools to enhance essential-gene analysis.