AbstractBackgroundThe discovery and development of antimicrobial drugs were one of the most significant advances in medicine, but the evolution of microbial resistance limited the efficiency of these drugs.AimThis paper reviews the collateral sensitivity in bacteria and its potential and limitation as a new target for treating infections.Results and DiscussionKnowledge mechanisms of resistance to antimicrobial agents are useful to trace a practical approach to treat and control of resistant pathogens. The effect of a resistance mechanism to certain antibiotics on the susceptibility or resistance to other drugs is a key point that may be helpful for applying a strategy to control resistance challenges. In an evolutionary trade‐off known as collateral sensitivity, the resistance mechanism to a certain drug may be mediated by the hypersensitivity to other drugs. Collateral sensitivity has been described for different drugs in various bacteria, but the molecular mechanisms affecting susceptibility are not well demonstrated. Collateral sensitivity could be studied to detect its potential in the battle against resistance crisis as well as in the treatment of pathogens adapting to antibiotics. Collateral sensitivity‐based antimicrobial therapy may have the potential to limit the emergence of antibiotic resistance.