The Disease Ontology (DO) is a comprehensive knowledge base of 8043 human diseases, designed to integrate and standardize disease and medical vocabularies. The DO web browser, built using a graph database and Lucene, enables efficient querying and semantic integration through cross-mapping with MeSH, ICD, NCI's thesaurus, SNOMED CT, and OMIM. DO is utilized by major biomedical databases and ontologies for disease annotation and representation. The DO project has been incorporated into open-source tools like Gene Answers and FunDO, facilitating the connection of gene and disease data. Future developments aim to enhance DO's representation and integration capabilities, including the expansion of logical definitions and cross-references to orthogonal ontologies. The DO paradigm is also extensible for creating non-human organism disease ontologies.The Disease Ontology (DO) is a comprehensive knowledge base of 8043 human diseases, designed to integrate and standardize disease and medical vocabularies. The DO web browser, built using a graph database and Lucene, enables efficient querying and semantic integration through cross-mapping with MeSH, ICD, NCI's thesaurus, SNOMED CT, and OMIM. DO is utilized by major biomedical databases and ontologies for disease annotation and representation. The DO project has been incorporated into open-source tools like Gene Answers and FunDO, facilitating the connection of gene and disease data. Future developments aim to enhance DO's representation and integration capabilities, including the expansion of logical definitions and cross-references to orthogonal ontologies. The DO paradigm is also extensible for creating non-human organism disease ontologies.