ClassyFire is a comprehensive, flexible, and computable chemical taxonomy (ChemOnt) developed by a team of researchers led by David S. Wishart. The taxonomy consists of over 4800 categories organized into up to 11 levels, with each category defined by unambiguous, computable structural rules. The ClassyFire web server and Ruby API provide automated structural classification of chemical compounds, using only their chemical structures and features. This tool has been used to annotate over 77 million compounds and integrate data from various sources, enhancing the understanding of chemical compounds and their biological properties. The development of ClassyFire addresses the lack of a standardized chemical ontology in chemistry, which has hindered the classification and annotation of chemical structures. The taxonomy and classification algorithm are designed to be open-source, fast, and fully automated, making it accessible to chemists and cheminformaticians for large-scale, rapid, and consistent chemical classification.ClassyFire is a comprehensive, flexible, and computable chemical taxonomy (ChemOnt) developed by a team of researchers led by David S. Wishart. The taxonomy consists of over 4800 categories organized into up to 11 levels, with each category defined by unambiguous, computable structural rules. The ClassyFire web server and Ruby API provide automated structural classification of chemical compounds, using only their chemical structures and features. This tool has been used to annotate over 77 million compounds and integrate data from various sources, enhancing the understanding of chemical compounds and their biological properties. The development of ClassyFire addresses the lack of a standardized chemical ontology in chemistry, which has hindered the classification and annotation of chemical structures. The taxonomy and classification algorithm are designed to be open-source, fast, and fully automated, making it accessible to chemists and cheminformaticians for large-scale, rapid, and consistent chemical classification.