Bacterial adaptation to antibiotics has been very successful and over the past decade the increase in antibiotic resistance has generated considerable medical problems. Even though many drug resistances confer a fitness cost, suggesting that they might disappear by reducing the volume of antibiotic use, increasing evidence obtained from laboratory and epidemiological studies indicate that several processes will act to cause long-term persistence of resistant bacteria. Compensatory evolution that ameliorates the costs of resistance, the occurrence of cost-free resistances and genetic linkage between non-selected and selected resistances will confer a stabilization of the resistant bacteria. Thus, it is of importance that we forcefully implement strategies to reduce the rate of appearance and spread of resistant bacteria to allow new drug discovery to catch up with bacterial resistance development.