The review discusses the emergence and spread of CTX-M extended-spectrum β-lactamases (ESBLs), which are a significant cause of resistance to β-lactam antibiotics in gram-negative bacteria. CTX-M enzymes were first discovered in the late 1980s and have since become widespread, particularly in South America, the Far East, and Eastern Europe. These enzymes confer high-level resistance to cefotaxime and ceftazidime, with varying levels of resistance to other β-lactams. The review highlights the genetic properties of CTX-M genes, their epidemiological distribution, and the phenotypic and biochemical characteristics of CTX-M ESBLs. It also explores the structural relationships between CTX-M enzymes and their evolutionary potential, noting that they may have a unique evolutionary trajectory compared to other ESBLs. The review emphasizes the importance of adapting detection methods to effectively monitor and control the spread of CTX-M enzymes.The review discusses the emergence and spread of CTX-M extended-spectrum β-lactamases (ESBLs), which are a significant cause of resistance to β-lactam antibiotics in gram-negative bacteria. CTX-M enzymes were first discovered in the late 1980s and have since become widespread, particularly in South America, the Far East, and Eastern Europe. These enzymes confer high-level resistance to cefotaxime and ceftazidime, with varying levels of resistance to other β-lactams. The review highlights the genetic properties of CTX-M genes, their epidemiological distribution, and the phenotypic and biochemical characteristics of CTX-M ESBLs. It also explores the structural relationships between CTX-M enzymes and their evolutionary potential, noting that they may have a unique evolutionary trajectory compared to other ESBLs. The review emphasizes the importance of adapting detection methods to effectively monitor and control the spread of CTX-M enzymes.