Broad spectrum antibiotics act against a wide range of disease-causing bacteria. However, their use may be associated with serious adverse reactions in patients. Inadequate antimicrobial treatment has been shown to increase mortality. Thus, it is essential to shorten the antibiotic treatment duration to the time necessary to fight the infection. The objectives of this review are to summarize the available options, controversies and evidence concerning the optimization of antibiotic therapy in ICUs; the options we have to achieve faster identification of the pathogen(s), to target the therapy, to use narrower spectrum antibiotics or to discontinue empirical antimicrobial treatment; and the options that are available to manage the treatment properly. Antibiotic de-escalation is a crucial strategy to minimize the risk of inadequate therapy as well as to decrease the risk of bacterial resistance development. Rapid tests and biomarkers may help to identify or rule out bacterial infections, helping clinicians to avoid unnecessary use of antibiotics and to shorten the treatment. These more accurate novel diagnostic tools can help us to improve patient outcomes.