Patient safety is one of the main research targets in various segments of the health field, so the clinical pharmacy has been contributing to patient-centered care to maximize therapy and minimize the risks of drug use. This study is a literature review that aimed to highlight the clinical pharmacy applied to pediatrics, as a humanization strategy on the policy of rational use of off-label drugs. As a methodological proposal, a clinical protocol was developed, from the perspective of clinical pharmacy in the use of off-label therapy in pediatrics, for use in hospital units, aimed at standardizing services, based on evidence. Finally, this research sought to highlight the role of the pharmacist in favor of the rational use of medicines, which from the clinical pharmacy is possible to mitigate possible problems related to medicines (PRMs), as well as to propose clinical pharmaceutical interventions, registered in the multi-professional medical records, in line with the optimization and conciliation of therapy aiming at the rational use of off-label drugs. Resulting in encouraging regional hospital establishments to develop clinical pharmacies, with the clinical pharmacist as a preceptor in the care process, encouraging the creation of clinical protocols, also promoting the pharmacovigilance service with the patient safety center in the hospital environment.