The containment of the phenomenon of resistance towards antimicrobials is a priority, especially in preserving molecules acting against Gram-negative pathogens, which represent the isolates more frequently found in the fragile population of patients admitted to Intensive Care Units. Antimicrobial therapy aims to prevent resistance through several actions, which are collectively known as “antimicrobial stewardship”, to be taken together, including the application of pharmacokinetic/pharmacodynamic (PK/PD) principles. PK/PD application has been shown to prevent the emergence of resistance in numerous experimental studies, although a straight translation to the clinical setting is not possible. Individualized antibiotic dosing and duration should be pursued in all patients, and even more especially when treating intensive care unit (ICU) septic patients in whom optimal exposure is both difficult to achieve and necessary. In this review, we report on the available data that support the application of PK/PD parameters to contain the development of resistance and we give some practical suggestions that can help to translate the benefit of PK/PD application to the bedside.