In the 21st century, the world is facing a post-antibiotic era, in which the appearance of infections with a minor or no therapeutic alternative is common. In this context, it is essential to implement measures that optimize the available therapeutic tool, thus generating new strategies that strengthen the fight against growing bacterial resistance. The evolutionary interactions suggest that the development of sensitivity or resistance of a microorganism to an antimicrobial will have an inverse effect (collateral sensitivity) or similar (cross resistance) in a second antimicrobial that is involved in this system. The evolutionary interactions are considered as a new mechanism of drug interaction, and additional, it establishes the collateral sensitivity as a therapeutic strategy to combat bacterial resistance, which could be integrated and evaluated in the future as a new strategy in the antimicrobial stewardship programs.