This review discusses the nomenclature for resistance determinants to macrolides, lincosamides, and streptogramin B (MLS_B) antibiotics. The authors propose a new system for naming MLS_B resistance genes, inspired by the rules used for tetracycline resistance genes. The system is based on the amino acid sequence identity between genes, with genes sharing ≥80% identity assigned the same letter designation. Genes with <80% identity receive different designations. The review highlights the diversity of MLS_B resistance mechanisms, including rRNA methylases, efflux systems, and other enzymes that modify or inactivate antibiotics. The rRNA methylases are the most studied, but other mechanisms also contribute to resistance. The authors emphasize the importance of a standardized nomenclature to avoid confusion and facilitate the identification and classification of resistance genes. The review also discusses the spread of resistance genes among bacterial species and the need for a unified naming system to track and understand the evolution of resistance. The proposed system aims to improve the clarity and consistency of gene naming, aiding in research and clinical applications.This review discusses the nomenclature for resistance determinants to macrolides, lincosamides, and streptogramin B (MLS_B) antibiotics. The authors propose a new system for naming MLS_B resistance genes, inspired by the rules used for tetracycline resistance genes. The system is based on the amino acid sequence identity between genes, with genes sharing ≥80% identity assigned the same letter designation. Genes with <80% identity receive different designations. The review highlights the diversity of MLS_B resistance mechanisms, including rRNA methylases, efflux systems, and other enzymes that modify or inactivate antibiotics. The rRNA methylases are the most studied, but other mechanisms also contribute to resistance. The authors emphasize the importance of a standardized nomenclature to avoid confusion and facilitate the identification and classification of resistance genes. The review also discusses the spread of resistance genes among bacterial species and the need for a unified naming system to track and understand the evolution of resistance. The proposed system aims to improve the clarity and consistency of gene naming, aiding in research and clinical applications.