Antibiotics are drugs widely used all around the world. Central nervous system adverse drug reactions (CNS ADRs) are mostly under-suspected with antibiotics. Nevertheless, these ADRs could lead to severe complications such as encephalopathy. To illustrate the clinical patterns of these off-target ADRs, we here present data from pharmacovigilance system, through different populations and points of view (worldwide, French population, vulnerable population and individual). These data could help clinicians to better know about CNS ADRs with antibiotics, to better identify risk factors and vulnerable patients and to highlight the importance to set up the right diagnostic explorations in the best timing to avoid complications. Clinicians should request a pharmacological opinion from pharmacologist (biologists and pharmacovigilance clinicians) in front of vulnerable population before or during antibiotics. Pharmacovigilance advice could help clinicians in the diagnosis and the management of an ADR. Therapeutic drug monitoring is particularly contributive to adjust doses of antibiotics administered in vulnerable patients. Pharmacovigilance advice and TDM are essential to perform personalized medicine, and contribute to the proper use of drugs.