"De-escalation therapy" is a term that suggests the need to reduce the spectrum or the number of antibiotics formerly prescribed for critical patients, upon clinical improvement and/or microorganism recovery. The major goal of this concept is the use of broad-spectrum antibiotic agents as initial drugs of choice for severe patients, instead of "reserving" the most potent agents after an inadequate clinical response, or after the microorganism is recovered. Despite possible commercial concerns and an unproven but possible relationship with enhancing global antibiotic use, the concept was correct and in accordance with scientific evidence. However, the "de-escalation" component of the concept is very seldom reported, and no large clinical trial on this issue is available until today. To definitely put in practice this concept, comparative large trials must be designed and sponsored to insert this strategy at the same level of evidence of wide initial empiric antibiotic treatments.