Whereas infections caused by multidrug-resistant micro-organisms are increasing worldwide, there are few new molecules, especially ones that are active against Gram-negative strains. There are extensive data showing that the administration of antimicrobials according to pharmacokinetic/pharmacodynamic parameters improves the possibility of a positive clinical outcome, particularly in severely ill patients. Evidence is growing that when pharmacokinetic/pharmacodynamic parameters are used to target not only clinical cure but also eradication, the spread of resistance will also be contained. The present paper summarizes the most relevant papers published in this field and provides some suggestions for dosing regimens that can be adopted in the clinical setting to limit the spread of resistance.