Important human pathogens resistant to antibiotics result from the human use of antibiotics. Does this imply that reducing their usage or removing antibiotics from medicine and agriculture will restore the effectiveness of these drugs? The authors argue that resistance evolution and susceptibility evolution are not, in a sense, just different sides of the same coin. Resistance genes acquire new functions and the initial costs of resistance can evolve into advantages. Decreasing drug use might not replace a fundamental change in drug design to avoid the evolution of resistant, and encourage the evolution of susceptible, microorganisms.