The Comprehensive Antibiotic Resistance Database (CARD) is a manually curated resource that provides high-quality reference data on the molecular basis of antimicrobial resistance (AMR). It is ontologically structured, model-centric, and covers a wide range of AMR drug classes and resistance mechanisms, including intrinsic, mutation-driven, and acquired resistance. CARD is built on the Antibiotic Resistance Ontology (ARO), a hierarchical controlled vocabulary that facilitates advanced data sharing and organization. Recent improvements include extensive curation of additional reference sequences and mutations, development of a unique Model Ontology (MO) and accompanying AMR detection models, new visualization tools, and expansion of the Resistance Gene Identifier (RGI) for detecting emergent AMR threats. CARD's curation is updated monthly through manual literature curation, computational text mining, and genome analysis. The database aims to address the molecular basis of AMR by creating an ontology- and model-based framework for curation and detection of known resistance genes, variants, and emerging threats.The Comprehensive Antibiotic Resistance Database (CARD) is a manually curated resource that provides high-quality reference data on the molecular basis of antimicrobial resistance (AMR). It is ontologically structured, model-centric, and covers a wide range of AMR drug classes and resistance mechanisms, including intrinsic, mutation-driven, and acquired resistance. CARD is built on the Antibiotic Resistance Ontology (ARO), a hierarchical controlled vocabulary that facilitates advanced data sharing and organization. Recent improvements include extensive curation of additional reference sequences and mutations, development of a unique Model Ontology (MO) and accompanying AMR detection models, new visualization tools, and expansion of the Resistance Gene Identifier (RGI) for detecting emergent AMR threats. CARD's curation is updated monthly through manual literature curation, computational text mining, and genome analysis. The database aims to address the molecular basis of AMR by creating an ontology- and model-based framework for curation and detection of known resistance genes, variants, and emerging threats.