The article discusses the development and clinical use of β-lactamase inhibitors over the past three decades. It begins by explaining the mechanism of action of β-lactam antibiotics, which target bacterial cell wall synthesis by inhibiting enzymes like penicillin-binding proteins (PBPs). However, resistance to these antibiotics has emerged due to the production of β-lactamases, enzymes that hydrolyze β-lactam antibiotics. To counteract this, two strategies have been developed: creating β-lactam antibiotics that resist enzymatic inactivation or using β-lactamase inhibitors to protect the β-lactam from degradation. The article classifies β-lactamases into four main categories (Ambler classes A-D) and discusses their mechanisms of action, including the hydrolytic processes that allow them to inactivate β-lactam antibiotics. It also highlights the development of β-lactamase inhibitors, such as clavulanic acid, sulbactam, and tazobactam, which inhibit β-lactamases and allow the β-lactam to reach its target. These inhibitors are used in combination with β-lactam antibiotics to enhance their efficacy against resistant bacteria. The article further explores the problem of resistance to β-lactamase inhibitors, particularly in class A β-lactamases, where certain substitutions in the enzyme can confer resistance. It also discusses the promise of novel β-lactamase inhibitors, including monobactam derivatives, penems, and other compounds that may extend the lifespan of current β-lactam antibiotics. The article concludes by emphasizing the importance of these inhibitors in the future of β-lactam therapy, as they can preserve existing antibiotics and may be used in conjunction with new β-lactam drugs. The review underscores the ongoing challenges in combating β-lactam resistance and the need for continued research into new inhibitors and strategies to combat this growing threat.The article discusses the development and clinical use of β-lactamase inhibitors over the past three decades. It begins by explaining the mechanism of action of β-lactam antibiotics, which target bacterial cell wall synthesis by inhibiting enzymes like penicillin-binding proteins (PBPs). However, resistance to these antibiotics has emerged due to the production of β-lactamases, enzymes that hydrolyze β-lactam antibiotics. To counteract this, two strategies have been developed: creating β-lactam antibiotics that resist enzymatic inactivation or using β-lactamase inhibitors to protect the β-lactam from degradation. The article classifies β-lactamases into four main categories (Ambler classes A-D) and discusses their mechanisms of action, including the hydrolytic processes that allow them to inactivate β-lactam antibiotics. It also highlights the development of β-lactamase inhibitors, such as clavulanic acid, sulbactam, and tazobactam, which inhibit β-lactamases and allow the β-lactam to reach its target. These inhibitors are used in combination with β-lactam antibiotics to enhance their efficacy against resistant bacteria. The article further explores the problem of resistance to β-lactamase inhibitors, particularly in class A β-lactamases, where certain substitutions in the enzyme can confer resistance. It also discusses the promise of novel β-lactamase inhibitors, including monobactam derivatives, penems, and other compounds that may extend the lifespan of current β-lactam antibiotics. The article concludes by emphasizing the importance of these inhibitors in the future of β-lactam therapy, as they can preserve existing antibiotics and may be used in conjunction with new β-lactam drugs. The review underscores the ongoing challenges in combating β-lactam resistance and the need for continued research into new inhibitors and strategies to combat this growing threat.