Antimicrobial agents are approaching the end of their effectiveness. The prevailing drug development strategy is based on a presumption that results in resistance: that disease can be cured by exploitation of the vulnerabilities in microbial reproduction. Although some did predict the evolution of resistance to such drugs, the mechanisms by which genes conferring resistance have spread was not predicted. The author argues that the mechanism of spread is a consequence of the chemotherapeutics themselves acting on the evolution of pathogens, and that for future drugs to remain effective they must avoid such effects.